Virus

A virus is a small, infectious agent that consists of a core of genetic material (either deoxyribonucleic acid [DNA] or ribonucleic acid [RNA]) surrounded by a shell of protein. Viruses cause disease by infecting a host cell and commandeering the host cell's synthetic capabilities to produce more viruses. The newly made viruses then leave the host cell, sometimes killing it in the process, and proceed to infect other cells within the host. Because viruses invade cells, no drug therapy has yet been designed to kill viruses. The human immune system is the only defense against a viral disease.

Viruses can infect both plants, bacteria , and animals. The tobacco mosaic virus, one of the most studied of all viruses, infects tobacco plants. Bacterial viruses, called bacteriophages, infect a variety of bacteria, such as Escherichia coli, a bacteria commonly found in the human digestive tract. Animal viruses cause a variety of fatal diseases. Acquired Immune Deficiency Syndrome (AIDS ) is caused by the Human Immunodeficiency Virus (HIV); hepatitis and rabies are viral diseases; and the socalled hemorrhagic fevers, which are characterized by severe internal bleeding, are caused by filoviruses. Other animal viruses cause some of the most common human diseases. Often, these diseases strike in childhood. Measles, mumps, and chickenpox are viral diseases. The common cold and influenza are also caused by viruses. Finally, some viruses can cause cancer and tumors. One such virus, Human T-cell Leukemia Virus (HTLV), was only recently discovered and its role in the development of a special kind of leukemia is still being elucidated.

Although viral structure varies considerably between the different types of viruses, all viruses share some common characteristics. All viruses contain either RNA or DNA surrounded by a protective protein shell called a capsid. Some viruses have a double strand of DNA, others a single strand of DNA. Other viruses have a double strand of RNA or a single strand of RNA. The size of the genetic material of viruses is often quite small. Compared to the 100,000 genes that exist within human DNA, viral genes number from 10 to about 200 genes.

Viruses contain such small amounts of genetic material because the only activity that they perform independently of a host cell is the synthesis of the protein capsid. In order to reproduce, a virus must infect a host cell and take over the host cell's synthetic machinery. This aspect of viruses—that the virus does not appear to be "alive" until it infects a host cell—has led to controversy in describing the nature of viruses. Are they living or non-living? When viruses are not inside a host cell, they do not appear to carry out many of the functions ascribed to living things, such as reproduction, metabolism , and movement. When they infect a host cell, they acquire these capabilities. Thus, viruses are both living and nonliving. It was once acceptable to describe viruses as agents that exist on the boundary between living and non-living; however, a more accurate description of viruses is that they are either active or inactive, a description that leaves the question of life behind altogether.

The origin of viruses is also controversial. Some viruses, such as the pox viruses, are so complex that they appear to have been derived from some kind of living eukaryote or prokaryote . The origin of the poxvirus could therefore resemble that of mitochondria and chloroplasts, organelles within eukaryotic cells which are thought to have once been independent organisms. On the other hand, some viruses are extremely simple in structure, leading to the conclusion that these viruses are derived from cellular genetic material that somehow acquired the capacity to exist independently. This possibility is much more likely for most viruses; however, scientists still believe that the poxvirus is the exception to this scenario.

Structure of viruses

All viruses consist of genetic material surrounded by a capsid, but within the broad range of virus types, variations exist within this basic structure. Studding the envelope of these viruses are protein "spikes." These spikes are clearly visible on some viruses, such as the influenza viruses; on other enveloped viruses, the spikes are extremely difficult to see. The spikes help the virus invade host cells. The influenza virus, for instance, has two types of spikes. One type, composed of hemagglutinin protein (HA), fuses with the host cell membrane , allowing the virus particle to enter the cell. The other type of spike, composed of the protein neuraminidase (NA), helps the newly formed virus particles to bud out from the host cell membrane.

The capsid of viruses is relatively simple in structure, owing to the few genes that the virus contains to encode the capsid. Most viral capsids consist of a few repeating protein subunits. The capsid serves two functions: it protects the viral genetic material and it helps the virus introduce itself into the host cell. Many viruses are extremely specific, targeting only certain cells within the plant or animal body. HIV, for instance, targets a specific immune cell, the T helper cell. The cold virus targets respiratory cells, leaving the other cells in the body alone. How does a virus "know" which cells to target? The viral capsid has special receptors that match receptors on their targeted host cells. When the virus encounters the correct receptors on a host cell, it "docks" with this host cell and begins the process of infection and replication.

Most viruses are rod- or roughly sphere-shaped. Rod-shaped viruses include tobacco mosaic virus and the filoviruses. Although they look like rods under a microscope , these viral capsids are actually composed of protein molecules arranged in a helix. Other viruses are shaped somewhat like spheres, although many viruses are not actual spheres. The capsid of the adenovirus, which infects the respiratory tract of animals, consists of 20 triangular faces. This shape is called a icosahedron. HIV is a true sphere , as is the influenza virus.

Some viruses are neither rod- or sphere-shaped. The poxviruses are rectangular, looking somewhat like bricks. Parapoxviruses are ovoid. Bacteriophages are the most unusually shaped of all viruses. A bacteriophage consists of a head region attached to a sheath. Protruding from the sheath are tail fibers that dock with the host bacterium. The bacteriophage's structure is eminently suited to the way it infects cells. Instead of the entire virus entering the bacterium, the bacteriophage injects its genetic material into the cell, leaving an empty capsid on the surface of the bacterium.

Viral infection

Viruses are obligate intracellular parasites , meaning that in order to replicate, they need to be inside a host cell. Viruses lack the machinery and enzymes necessary to reproduce; the only synthetic activity they perform on their own is to synthesize their capsids.

The infection cycle of most viruses follows a basic pattern. Bacteriophages are unusual in that they can infect a bacterium in two ways (although other viruses may replicate in these two ways as well). In the lytic cycle of replication, the bacteriophage destroys the bacterium it infects. In the lysogenic cycle, however, the bacteriophage coexists with its bacterial host, and remains inside the bacterium throughout its life, reproducing only when the bacterium itself reproduces.

An example of a bacteriophage that undergoes lytic replication inside a bacterial host is the T4 bacteriophage which infects E. coli. T4 begins the infection cycle by docking with an E. coli bacterium. The tail fibers of the bacteriophage make contact with the cell wall of the bacterium, and the bacteriophage then injects its genetic material into the bacterium. Inside the bacterium, the viral genes are transcribed. One of the first products produced from the viral genes is an enzyme that destroys the bacterium's own genetic material. Now the virus can proceed in its replication unhampered by the bacterial genes. Parts of new bacteriophages are produced and assembled. The bacterium then bursts, and the new bacteriophages are freed to infect other bacteria. This entire process takes only 20-30 minutes.

In the lysogenic cycle, the bacteriophage reproduces its genetic material but does not destroy the host's genetic material. The bacteriophage called lambda, another E. coli-infecting virus, is an example of a bacteriophage that undergoes lysogenic replication within a bacterial host. After the viral DNA has been injected into the bacterial host, it assumes a circular shape. At this point, the replication cycle can either become lytic or lysogenic. In a lysogenic cycle, the circular DNA attaches to the host cell genome at a specific place. This combination host-viral genome is called a prophage. Most of the viral genes within the prophage are repressed by a special repressor protein, so they do not encode the production of new bacteriophages. However, each time the bacterium divides, the viral genes are replicated along with the host genes. The bacterial progeny are thus lysogenically infected with viral genes.

Interestingly, bacteria that contain prophages can be destroyed when the viral DNA is suddenly triggered to undergo lytic replication. Radiation and chemicals are often the triggers that initiate lytic replication. Another interesting aspect of prophages is the role they play in human diseases. The bacteria that cause diphtheria and botulism both harbor viruses. The viral genes encode powerful toxins that have devastating effects on the human body. Without the infecting viruses, these bacteria may well be innocuous. It is the presence of viruses that makes these bacterial diseases so lethal.

Types of viruses

Scientists have classified viruses according to the type of genetic material they contain. Broad categories of viruses include double-stranded DNA viruses, single-stranded DNA viruses, double-stranded RNA viruses, and single stranded RNA viruses. For the description of virus types that follows, however, these categories are not used. Rather, viruses are described by the type of disease they cause.

Poxviruses

Poxviruses are the most complex kind of viruses known. They have large amounts of genetic material and fibrils anchored to the outside of the viral capsid that assist in attachment to the host cell. Poxviruses contain a double strand of DNA.

Viruses cause a variety of human diseases, including smallpox and cowpox. Because of worldwide vaccination efforts, smallpox has virtually disappeared from the world, with the last known case appearing in Somalia in 1977. The only places on Earth where smallpox virus currently exists are two labs: the Centers for Disease Control in Atlanta and the Research Institute for Viral Preparation in Moscow. Prior to the eradication efforts begun by the World Health Organization in 1966, smallpox was one of the most devastating of human diseases. In 1707, for instance, an outbreak of smallpox killed 18,000 of Iceland's 50,000 residents. In Boston in 1721, smallpox struck 5,889 of the city's 12,000 inhabitants, killing 15% of those infected.

Edward Jenner (1749-1823) is credited with developing the first successful vaccine against a viral disease, and that disease was smallpox. A vaccine works by eliciting an immune response. During this immune response, specific immune cells, called memory cells, are produced that remain in the body long after the foreign microbe present in a vaccine has been destroyed. When the body again encounters the same kind of microbe, the memory cells quickly destroy the microbe. Vaccines contain either a live, altered version of a virus or bacteria, or they contain only parts of a virus or bacteria, enough to elicit an immune response.

In 1797, Jenner developed his smallpox vaccine by taking pus from a cowpox lesion on the hand of a milkmaid. Cowpox was a common disease of the era, transmitted through contact with an infected cow. Unlike smallpox, however, cowpox is a much milder disease. Using the cowpox pus, he inoculated an eight-year-old boy. Jenner continued his vaccination efforts through his lifetime. Until 1976, children were vaccinated with the smallpox vaccine, called vaccinia. Reactions to the introduction of the vaccine ranged from a mild fever to severe complications, including (although very rarely) death. In 1976, with the eradication of smallpox complete, vaccinia vaccinations for children were discontinued, although vaccinia continues to be used as a carrier for recombinant DNA techniques. In these techniques, foreign DNA is inserted in cells. Efforts to produce a vaccine for HIV, for instance, have used vaccinia as the vehicle that carries specific parts of HIV.

Herpesviruses

Herpesviruses are enveloped, double-stranded DNA viruses. Of the more than 50 herpes viruses that exist, only eight cause disease in humans. These include the human herpes virus types 1 and 2 that cause cold sores and genital herpes; human herpes virus 3, or varicellazoster virus (VZV), that causes chicken pox and shingles ; cytomegalovirus (CMV), a virus that in some individuals attacks the cells of the eye and leads to blindness; human herpes virus 4, or Epstein-Barr virus (EBV), which has been implicated in a cancer called Burkitt's lymphoma; and human herpes virus types 6 and 7, newly discovered viruses that infect white blood cells. In addition, herpes B virus is a virus that infects monkeys and can be transmitted to humans by handling infected monkeys.

Adenoviruses

Adenoviruses are viruses that attack respiratory, intestinal, and eye cells in animals. More than 40 kinds of human adenoviruses have been identified. Adenoviruses contain double-stranded DNA within a 20-faceted capsid.

Adenoviruses that target respiratory cells cause bronchitis , pneumonia , and tonsillitis . Gastrointestinal illnesses caused by adenoviruses are usually characterized by diarrhea and are often accompanied by respiratory symptoms. Some forms of appendicitis are also caused by adenoviruses. Eye illnesses caused by adenoviruses include conjunctivitis, an infection of the eye tissues, as well as a disease called pharyngoconjunctival fever, a disease in which the virus is transmitted in poorly chlorinated swimming pools.

Papoviruses

Human papoviruses include two groups: the papilloma viruses and the polyomaviruses. Human papilloma viruses (HPV) are the smallest double-stranded DNA viruses. They replicate within cells through both the lytic and the lysogenic replication cycles. Because of their lysogenic capabilities, HPV-containing cells can be produced through the replication of those cells that HPV initially infects. In this way, HPV infects epithelial cells, such as the cells of the skin. HPVs cause several kinds of benign (non-cancerous) warts, including plantar warts (those that form on the soles of the feet) and genital warts. However, HPVs have also been implicated in a form of cervical cancer that accounts for 7% of all female cancers.

HPV is believed to contain oncogenes, or genes that encode for growth factors that initiate the uncontrolled growth of cells. This uncontrolled proliferation of cells is called cancer. When the HPV oncogenes within an epithelial cell are activated, they cause the epithelial cell to proliferate. In the cervix (the opening of the uterus), the cell proliferation manifests first as a condition called cervical neoplasia. In this condition, the cervical cells proliferate and begin to crowd together. Eventually, cervical neoplasia can lead to full-blown cancer.

Polyomaviruses are somewhat mysterious viruses. Studies of blood have revealed that 80% of children aged five to nine years have antibodies to these viruses, indicating that they have at some point been exposed to polyomaviruses. However, it is not clear what disease this virus causes. Some evidence exists that a mild respiratory illness is present when the first antibodies to the virus are evident. The only disease that is certainly caused by polyomavirses is called progressive multifocal leukoencephalopathy (PML), a disease in which the virus infects specific brain cells called the oligodendrocytes. PML is a debilitating disease that is usually fatal, and is marked by progressive neurological degeneration. It usually occurs in people with suppressed immune systems, such as cancer patients and people with AIDS.

Hepadnaviruses

The hepadnaviruses cause several diseases, including hepatitis B. Hepatitis B is a chronic, debilitating disease of the liver and immune system. The disease is much more serious than hepatitis A for several reasons: it is chronic and long-lasting; it can cause cirrhosis and cancer of the liver; and many people who contract the disease become carriers of the virus, able to transmit the virus through body fluids such as blood, semen, and vaginal secretions.

The hepatitis B virus (HBV) infects liver cells and has one of the smallest viral genomes. A double-stranded DNA virus, HBV is able to integrate its genome into the host cell's genome. When this integration occurs, the viral genome is replicated each time the cell divides. Individuals who have integrated HBV into their cells become carriers of the disease. Recently, a vaccine against

HBV was developed. The vaccine is especially recommended for health care workers who through exposure to patient's body fluids are at high risk for infection.

Parvoviruses

Parvoviruses are icosahedral, single-stranded DNA viruses that infect a wide variety of mammals . Each type of parvovirus has its own host. For instance, one type of parvovirus causes disease in humans; another type causes disease in cats ; while still another type causes disease in dogs. The disease caused by parvovirus in humans is called erythremia infectiosum, a disease of the red blood cells that is relatively rare except for individuals who have the inherited disorder sickle cell anemia . Canine and feline parvovirus infections are fatal, but a vaccine against parvovirus is available for dogs and cats.

Orthomyxoviruses

Orthomyxoviruses cause influenza ("flu"). This highly contagious viral infection can quickly assumeepidemic proportions, given the right environmental conditions. An influenza outbreak is considered an epidemic when more than 10% of the population is infected. In 1918, the influenza virus infected 25 million Americans and killed 22 million people worldwide in 18 months. Most people who require hospitalization due to influenza or who die from the infection are elderly individuals, especially those with a pre-existing chronic lung or heart condition. The most common complication of influenza is pneumonia.

Influenza viruses are spherical, single-stranded RNA viruses, with visible protein spikes that protrude from the capsid. Three strains of influenza virus—strains A, B, and C—cause illness in humans. Strain C causes a relatively mild illness that usually does not balloon into an epidemic. Strains A and B cause more debilitating illnesses and are the frequent cause of epidemics. These strains undergo frequent genetic mutation , so that antibodies that are made in the body against prior strains are ineffective against mutated strains. Strain A is the most common influenza virus; strain B emerges only once every two to four years.

A vaccine against the current strain of influenza is prepared each year. This vaccination should be performed during the fall months, so that antibodies against the virus reach optimum numbers by the winter flu season. For reasons that are not clear, flu vaccinations are only 50-60% effective in children, while in the elderly, they can be 70-90% effective. Therefore, most experts recommend that the elderly, who are most at risk for developing serious complications from flu, receive a flu vaccination every year.

Enteroviruses

The enteroviruses are icosahedral, enveloped, single-stranded RNA viruses. Five types of enteroviruses cause diseases in humans, including the polioviruses (which cause polio) and echoviruses (which cause viral meningitis ). Enteroviruses have an unusual replication cycle. They first enter the body through the upper respiratory tract and replicate within respiratory cells. Once the virus particles have been replicated, they are shed back into the oral secretions and are then swallowed. In the gastrointestinal tract, more replication takes place, and the viruses then enter the bloodstream. From the bloodstream, the viruses are carried to all parts of the body. However, further replication takes place only in cells for which the virus has an affinity. For example, polioviruses enter the nerve cells in the brain. There, viruses undergo further replication, and symptoms begin to appear.

Polio, the disease caused by polioviruses, is now controlled in the United States and other developed countries by the polio vaccine. However, before the introduction of this vaccine in the late 1950s, polio was one of the most feared human diseases. It causes a widespread paralysis of the muscles, sometimes including those of the respiratory system . Prolonged breathing assistance is needed for those individuals in which the respiratory muscles are paralyzed.

Echoviruses, another kind of enterovirus, cause viral meningitis, an inflammation of the nervous system . This disease is not as serious as the meningitis caused by bacteria, called bacterial meningitis.

Rhinoviruses

Rhinoviruses (from the Latin word meaning "nose") cause the common cold. They come from the same family as the enteroviruses, described above, and thus contain a single strand of RNA enclosed within an enveloped, 20-sided capsid. Interestingly, 113 types of rhinoviruses have been classified. These 113 types differ slightly in the composition of their capsids, so antibodies that are made against one type of rhinovirus are often ineffective against other types of viruses. For this reason, most people are susceptible to colds from season to season.

Paramyxoviruses

These helical, enveloped, single-stranded RNA viruses cause pneumonia, croup, measles, and mumps in children. A vaccine against measles and mumps has greatly reduced the incidence of these diseases in the United States. In addition, a paramyxovirus called respiratory syncytial virus (RSV) causes bronchiolitis (an infection of the bronchioles) and pneumonia.

Flaviviruses

Flaviviruses (from the Latin word meaning "yellow") cause insect-carried diseases including yellow fever , an often fatal disease characterized by high fever and internal bleeding. Flaviviruses are single-stranded RNA viruses.

Filoviruses

The two filoviruses, Ebola virus and Marburg virus, are perhaps the most lethal of all human viruses. Both cause severe fevers accompanied by internal bleeding, which eventually kills the victim. The fatality rate of Marburg is about 60%, while the fatality rate of Ebolavirus is about 90%. Both are transmitted through contact with body fluids. Marburg and Ebola also infect primates .

Rhabdoviruses

Rhabdoviruses are bullet-shaped, single-stranded RNA viruses. They are responsible for rabies, a disease that affects dogs, rodents , and humans.

Retroviruses

Retroviruses are unique viruses. They are double-stranded RNA viruses that contain an enzyme called reverse transcriptase. Within the host cell, the virus uses reverse transcriptase to make a DNA copy from its RNA genome. In all other organisms, RNA is synthesized from DNA. Cells infected with retroviruses are the only living things that reverse this process.

The first retroviruses discovered were viruses that infect chickens. The Rous sarcoma virus, discovered in the 1950s by Peyton Rous (1879-1970), was also the first virus that was linked to cancer. But it was not until 1980 that the first human retrovirus was discovered. Called Human T-cell Leukemia Virus (HTLV), this virus causes a form of leukemia called adult T-cell leukemia. In 1983-4, another human retrovirus, Human Immunodefiency Virus, the virus responsible for AIDS, was discovered independently by two researchers. Both HIV and HTLV are transmitted in body fluids.

See also Childhood diseases; Cold, common; Meningitis; Poliomyelitis.

Resources

books

Doerfler, Walter, and Petra Bohm, eds. Virus Strategies: Molecular Biology and Pathenogenesis. New York: VCH, 1993.

Flint, S.J., et al. Principles of Virology: Molecular Biology,Pathogenesis, and Control. Washington: American Society for Microbiology, 1999.

Kurstak, Edouard, ed. Control of Virus Diseases. New York: Marcel Dekker, 1993.

Richman, D.D., and R.J. Whitley. Clinical Virology. 2nd ed. Washington: American Society for Microbiology, 2002.

Thomas, D. Brian. Viruses and the Cellular Immune Response. New York: Marcel Dekker, 1993.

periodicals

Appleton, Hazel. "Foodborne Viruses." The Lancet 336 (December 1990): 1362.

Berns, Kenneth I., and Michael R. Linden. "The Cryptic Life Style of Adeno-associated Virus." BioEssays 17 (March 1995): 237.

Bloch, Alan B., et al. "Recovery of Hepatitis A Virus from a Water Supply Responsible for a Common Source Outbreak of Hepatitis A." American Journal of Public Health 80 (April 1990): 428.

Cimons, M. "New Prospects on the HIV Vaccine Scene." ASMNews no. 68 (January 2002): 19-22.

Dutton, Gail. "Biotechnology Counters Bioterrorism." GeneticEngineering News no. 21 (December 2000): 1-22ff.

Dybul, M., T.-K. Chun, C. Yoder, et al. "Short-cycle Structured Intermittent Treatment of Chronic HIV Infection with Highly Effective Antiretroviral Therapy: Effects on Virologic, Immunologic, and Toxicity Parameters." Proceedings of the National Academy of Sciences no. 98 (18 December 2001): 15161-15166.

Ganem, Don. "Oncogenic Viruses: Of Marmots and Men." Nature 347 (September 20, 1990): 230.

Slater, P. E., et al. "Poliomyelitis Outbreak in Israel in 1988: A Report with Two Commentaries." The Lancet: 335 (May 19, 1992): 1192.

Zur Hausen, Harald. "Viruses in Human Cancer." Science 254 (November 22, 1991): 1167.

Kathleen Scogna

KEY TERMS

Bacteriophage

—A virus that infects bacteria.

Capsid

—The outer protein coat of a virus.

Deoxyribonucleic acid (DNA)

—The genetic material in a cell; in the nucleus, DNA transcribes RNA for the synthesis of proteins.

Envelope

—The outermost covering of some viruses; it is composed of lipid and protein acquired from the host cell's plasma membrane as the virus buds out from the cell.

Eukaryote

—A cell whose genetic material is carried on chromosomes inside a nucleus encased in a membrane. Eukaryotic cells also have organelles that perform specific metabolic tasks and are supported by a cytoskeleton which runs through the cytoplasm, giving the cell form and shape.

Exocytosis

—The process by which a virus "buds out" from the host cell.

Genome

—The complete sequence of genes within a cell or virus.

Host cell

—The specific cell that a virus targets and infects.

Icosahedron

—A 20–sided polyhedron.

Lysogenic cycle

—A viral replication cycle in which the virus does not destroy the host cell but co-exists within it.

Lytic cycle

—A viral replication cycle in which the virus destroys the host cell.

Obligate intracellular parasite

—An organism or agent, such as a virus, that cannot reproduce unless it is inside a cell.

Oncogene

—A gene that encodes for growth factors; oncogenes are believed to cause the cancerous growth of cells.

Prokaryote

—A type of cell without a true nucleus, such as a bacterium.

Retrovirus

—A type of virus that inserts its genetic material into the chromosomes of the cells it infects.

Reverse transcriptase

—The enzyme that allows a retrovirus to transcribe DNA from RNA.

Ribonucleic acid

—RNA; the molecule translated from DNA in the nucleus that directs protein synthesis in the cytoplasm; it is also the genetic material of many viruses.

Virus

Structure of viruses

Viral infection

Types of viruses

Resources

A virus is a small, infectious agent that consists of a core of genetic material (either deoxyribonucleic acid [DNA] or ribonucleic acid [RNA]) surrounded by a shell of protein. Viruses cause disease by infecting a host cell and commandeering the host cell’s synthetic capabilities to produce more viruses. The newly made viruses then leave the host cell, sometimes killing it in the process, and proceed to infect other cells within the host. Because viruses invade cells, no drug therapy has yet been designed to kill viruses. The human immune system is the only defense against a viral disease.

Viruses can infect both plants, bacteria, and animals. The tobacco mosaic virus, one of the most studied of all viruses, infects tobacco plants. Bacterial viruses, called bacteriophages, infect a variety of bacteria, such as Escherichia coli, a bacteria commonly found in the human digestive tract. Animal viruses cause a variety of fatal diseases. Acquired Immune Deficiency Syndrome (AIDS) is caused by the Human Immunodeficiency Virus (HIV); hepatitis and rabies are viral diseases; and the so-called hemorrhagic fevers, which are characterized by severe internal bleeding, are caused by filoviruses. Other animal viruses cause some of the most common human diseases. Often, these diseases strike in childhood. Measles, mumps, and chickenpox are viral diseases. The common cold and influenza are also caused by viruses. Finally, some viruses can cause cancer and tumors. One such virus, Human T-cell Leukemia Virus (HTLV), was only recently discovered and its role in the development of a special kind of leukemia is still being elucidated.

Structure of viruses

Although viral structure varies considerably between the different types of viruses, all viruses share some common characteristics. All viruses contain either RNA or DNA surrounded by a protective protein shell called a capsid. Some viruses have a double strand of DNA, others a single strand of DNA. Other viruses have a double strand of RNA or a single strand of RNA. The size of the genetic material of viruses is often quite small. Compared to the 100,000 genes that exist within human DNA, viral genes number from 10 to about 200 genes.

The capsid of viruses is relatively simple in structure, owing to the few genes that the virus contains to encode the capsid. Most viral capsids consist of a few repeating protein subunits. The capsid serves two functions: it protects the viral genetic material and it helps the virus introduce itself into the host cell. Many viruses are extremely specific, targeting only certain cells within the plant or animal body. HIV, for instance, targets a specific immune cell, the T helper cell. The cold virus targets respiratory cells, leaving the other cells in the body alone. How a virus was capable of this degree of recognition involves special receptors on the viral cpasid surface that match receptors on their targeted host cells. When the virus encounters the correct receptors on a host cell, it docks with this host cell and begins the process of infection and replication.

Most viruses are rod-shaped or roughly sphere-shaped. Rod-shaped viruses include tobacco mosaic virus and the filoviruses. Although they look like rods under a microscope, these viral capsids are actually composed of protein molecules arranged in a helix. Other viruses are shaped somewhat like spheres, although many viruses are not actual spheres. The capsid of the adenovirus, which infects the respiratory tract of animals, consists of 20 triangular faces. This shape is called an icosahedron. HIV is a true sphere, as is the influenza virus.

Some viruses are neither rod- nor sphere-shaped. The poxviruses are rectangular, looking somewhat like bricks. Parapoxviruses are ovoid. Bacteriophages are the most unusually shaped of all viruses. A bacteriophage consists of a head region attached to a sheath. Protruding from the sheath are tail fibers that dock with the host bacterium. Bacteriophage structure is eminently suited to the way it infects cells. Instead of the entire virus entering the bacterium, the bacteriophage injects its genetic material into the cell, leaving an empty capsid on the surface of the bacterium.

All viruses consist of genetic material surrounded by a capsid; but variations exist within this basic structure. Studding the envelope of these viruses are protein spikes. These spikes are clearly visible on some viruses, such as the influenza viruses; on other enveloped viruses, the spikes are extremely difficult to see. The spikes help the virus invade host cells. The influenza virus, for instance, has two types of spikes. One

type, composed of hemagglutinin protein, fuses with the host cell membrane, allowing the virus particle to enter the cell. The other type of spike, composed of the protein neuraminidase, helps the newly formed virus particles to bud out from the host cell membrane.

Viruses contain such small amounts of genetic material because the only activity that they perform independently of a host cell is the synthesis of the protein capsid. In order to reproduce, a virus must infect a host cell and take over the host cell’s synthetic machinery. This aspect of viruses—that the virus does not appear to be “alive” until it infects a host cell—has led to controversy in describing the nature of viruses. Are they living or non-living? When viruses are not inside a host cell, they do not appear to carry out many of the functions ascribed to living things, such as reproduction, metabolism, and movement. When they infect a host cell, they acquire these capabilities. Thus, viruses are both living and non-living. It was once acceptable to describe viruses as agents that exist on the boundary between living and non-living; however, a more accurate description of viruses is that they are either active or inactive, a description that leaves the question of life behind altogether.

The origin of viruses is also controversial. Some viruses, such as the pox viruses, are so complex that they appear to have been derived from some kind of living eukaryote or prokaryote. The origin of the pox-virus could therefore resemble that of mitochondria and chloroplasts, organelles within eukaryotic cells which are thought to have once been independent organisms. On the other hand, some viruses are extremely simple in structure, leading to the conclusion that these viruses are derived from cellular genetic material that somehow acquired the capacity to exist independently. This possibility is much more likely for most viruses; however, scientists still believe that the poxvirus is the exception to this scenario.

Viral infection

Viruses are obligate intracellular parasites, meaning that in order to replicate, they need to be inside a host cell. Viruses lack the machinery and enzymes necessary to reproduce; the only synthetic activity they perform on their own is to synthesize their capsids.

The infection cycle of most viruses follows a basic pattern. First, the virus docks with the host cell. The genetic material of the virus then enters the host cell and the virus loses its capsid. Once inside the host cell, the viral RNA or DNA takes over the cellular machinery to make more viruses. Viral subunits are produced, which are then assembled to make whole viruses. Finally, the new viruses leave the host cell, either by exocytosis or by destroying the host cell.

Bacteriophages are unusual in that they can infect a bacterium in two ways (although other viruses may replicate in these two ways as well). In the lytic cycle of replication, the bacteriophage destroys the bacterium it infects. In the lysogenic cycle, however, the bacteriophage coexists with its bacterial host, and remains inside the bacterium throughout its life, reproducing only when the bacterium itself reproduces.

An example of a bacteriophage that undergoes lytic replication inside a bacterial host is the T4

bacteriophage which infects E. coli. T4 begins the infection cycle by docking with an E. coli bacterium. The tail fibers of the bacteriophage make contact with the cell wall of the bacterium, and the bacteriophage then injects its genetic material into the bacterium. Inside the bacterium, the viral genes are transcribed. One of the first products produced from the viral genes is an enzyme that destroys the bacterium’s own genetic material. Now, the virus can proceed in its replication unhampered by the bacterial genes. Parts of new bacteriophages are produced and assembled. The bacterium then bursts, and the new bacteriophages are freed to infect other bacteria. This entire process takes only 20-30 minutes.

In the lysogenic cycle, the bacteriophage reproduces its genetic material but does not destroy the host’s genetic material. The bacteriophage called lambda, another E. coli -infecting virus, is an example of a bacteriophage that undergoes lysogenic replication within a bacterial host. After the viral DNA has been

injected into the bacterial host, it assumes a circular shape. At this point, the replication cycle can either become lytic or lysogenic. In a lysogenic cycle, the circular DNA attaches to the host cell genome at a specific place. This combination host-viral genome is called a prophage. Most of the viral genes within the prophage are repressed by a special repressor protein, so they do not encode the production of new bacteriophages. However, each time the bacterium divides, the viral genes are replicated along with the host genes. The bacterial progeny are thus lysogenically infected with viral genes.

Interestingly, bacteria that contain prophages can be destroyed when the viral DNA is suddenly triggered to undergo lytic replication. Radiation and chemicals are often the triggers that initiate lytic replication. Another interesting aspect of prophages is the role they play in human diseases. The bacteria that cause diphtheria and botulism both harbor viruses. The viral genes encode powerful toxins that have devastating effects on the human body. Without the infecting viruses, these bacteria may well be innocuous. It is the presence of viruses that makes these bacterial diseases so lethal.

Types of viruses

Scientists have classified viruses according to the type of genetic material they contain. Broad categories of viruses include double-stranded DNA viruses, single-stranded DNA viruses, double-stranded RNA viruses, and single stranded RNA viruses.

Poxviruses are the most complex kind of viruses known. They have large amounts of genetic material and fibrils anchored to the outside of the viral capsid that assist in attachment to the host cell. Poxviruses contain a double strand of DNA.

Herpesviruses are enveloped, double-stranded DNA viruses. Of the more than 50 herpes viruses that exist, only eight cause disease in humans. These include the human herpes virus types 1 and 2 that cause cold sores and genital herpes; human herpes virus 3, or varicella-zoster virus (VZV), that causes chickenpox and shingles; cytomegalovirus, a virus that in some individuals attacks the cells of the eye and leads to blindness; human herpes virus 4, or Epstein-Barr virus, which has been implicated in a cancer called Burkitt’s lymphoma; and human herpes virus types 6 and 7, newly discovered viruses that infect white blood cells. In addition, herpes B virus is a virus that infects monkeys and can be transmitted to humans by handling infected monkeys.

Adenoviruses are viruses that attack respiratory, intestinal, and eye cells in animals. More than 40 kinds of human adenoviruses have been identified. Adenoviruses contain double-stranded DNA within a 20-faceted capsid. Adenoviruses that target respiratory cells cause bronchitis, pneumonia, and tonsillitis. Gastrointestinal illnesses caused by adenoviruses are usually characterized by diarrhea and are often accompanied by respiratory symptoms. Some forms of appendicitis are also caused by adenoviruses. Eye illnesses caused by adenoviruses include conjunctivitis, an infection of the eye tissues, as well as a disease called pharyngoconjunctival fever, a disease in which the virus is transmitted in poorly chlorinated swimming pools.

Human papoviruses include two groups: the papilloma viruses and the polyomaviruses. Human papoviruses are the smallest double-stranded DNA viruses. They replicate within cells through both the lytic and the lysogenic replication cycles. Because of their lysogenic capabilities, human papilloma virus-containing cells can be produced through the replication of those cells that the virus initially infects. In this way, human papoviruses infect epithelial cells, such as the cells of the skin. The viruses cause several kinds of benign (non-cancerous) warts, including plantar warts (those that form on the soles of the feet) and genital warts. However, these viruses have also been implicated in a form of cervical cancer that accounts for slightly less than 10% of all female cancers.

Human papoviruses contain oncogenes, or genes that encode for growth factors that initiate the uncontrolled growth of cells. This uncontrolled proliferation of cells is called cancer. When the oncogenes within an epithelial cell are activated, they cause the epithelial cell to proliferate. In the cervix (the opening of the uterus), the cell proliferation manifests first as a condition called cervical neoplasia. In this condition, the cervical cells proliferate and begin to crowd together. Eventually, cervical neoplasia can lead to full-blown cancer.

Polyomaviruses are somewhat mysterious viruses. Studies of blood have revealed that 80% of children aged five to none years have antibodies to these viruses, indicating that they have at some point been exposed to polyomaviruses. However, it is not clear what disease this virus causes. Some evidence exists that a mild respiratory illness is present when the first antibodies to the virus are evident. The only disease that is certainly caused by polyomavirses is called progressive multifocal leukoencephalopathy, a disease in which the virus infects specific brain cells called the oligodendrocytes. This malady is a debilitating disease that is usually fatal, and is marked by progressive neurological degeneration. It usually occurs in people with suppressed immune systems, such as cancer patients and people with AIDS.

The hepadnaviruses cause several diseases, including hepatitis B. Hepatitis B is a chronic, debilitating disease of the liver and immune system. The disease is much more serious than hepatitis A for several reasons: it is chronic and long-lasting; it can cause cirrhosis and cancer of the liver; and many people who contract the disease become carriers of the virus, able to transmit the virus through body fluids such as blood, semen, and vaginal secretions.

The hepatitis B virus infects liver cells and has one of the smallest viral genomes. A double-stranded DNA virus, Hepatitis B virus is able to integrate its genome into the host cell’s genome. When this integration occurs, the viral genome is replicated each time the cell divides. Individuals who have integrated hepatitis B virus into their cells become carriers of the disease. Recently, a vaccine against hepatitis B was developed. The vaccine is especially recommended for health care workers who through exposure to patient’s body fluids are at high risk for infection.

Parvoviruses are icosahedral, single-stranded DNA viruses that infect a wide variety of mammals. Each type of parvovirus has its own host. For instance, one type of parvovirus causes disease in humans; another type causes disease in cats; while still another type causes disease in dogs. The disease caused by parvovirus in humans is called erythremia infectiosum, a disease of the red blood cells that is relatively rare except for individuals who have the inherited disorder sickle-cell anemia. Canine and feline parvovirus infections are fatal, but a vaccine against parvo-virus is available for dogs and cats.

Orthomyxoviruses cause influenza (flu). This highly contagious viral infection can quickly assume epidemic proportions, given the right environmental conditions. An influenza outbreak is considered an epidemic when more than 10% of the population is infected. Antibodies that are made against one type of rhinovirus are often ineffective against other types of viruses. For this reason, most people are susceptible to colds from season to season.

These helical, enveloped, single-stranded RNA viruses cause pneumonia, croup, measles, and mumps in children. A vaccine against measles and mumps has greatly reduced the incidence of these diseases in the United States. In addition, a paramyxovirus called respiratory syncytial virus (RSV) causes bronchiolitis (an infection of the bronchioles) and pneumonia.

Flaviviruses (from the Latin word meaning yellow) cause insect-carried diseases including yellow fever, an often-fatal disease characterized by high fever and internal bleeding. Flaviviruses are single-stranded RNA viruses.

The two filoviruses, Ebola virus and Marburg virus, are among the most lethal of all human viruses. Both cause severe fevers accompanied by internal bleeding, which eventually kills the victim. The fatality rate of Marburg is about 60%, while the fatality rate of Ebola virus approaches 90%. Both are transmitted through contact with body fluids. Marburg and Ebola also infect primates. Study of these viruses is limited because the outbreaks appear quickly and disappear just as quickly, and because laboratory study requires a facility that is “escape-proof” for the virus; only a handful of such facilities exist worldwide as of 2006

KEY TERMS

Bacteriophage —A virus that infects bacteria.

Capsid —The outer protein coat of a virus.

Deoxyribonucleic acid (DNA) —The genetic material in a cell; in the nucleus, DNA transcribes RNA for the synthesis of proteins.

Envelope —The outermost covering of some viruses; it is composed of lipid and protein acquired from the host cell’s plasma membrane as the virus buds out from the cell.

Eukaryote —A cell whose genetic material is carried on chromosomes inside a nucleus encased in a membrane. Eukaryotic cells also have organelles that perform specific metabolic tasks and are supported by a cytoskeleton which runs through the cytoplasm, giving the cell form and shape.

Exocytosis —The process by which a virus “buds out” from the host cell.

Genome —The complete sequence of genes within a cell or virus.

Host cell —The specific cell that a virus targets and infects.

Icosahedron —A 20–sided polyhedron.

Lysogenic cycle —A viral replication cycle in which the virus does not destroy the host cell but co-exists within it.

Lytic cycle —A viral replication cycle in which the virus destroys the host cell.

Obligate intracellular parasite —An organism or agent, such as a virus, that cannot reproduce unless it is inside a cell.

Oncogene —A gene that encodes for growth factors; oncogenes are believed to cause the cancerous growth of cells.

Prokaryote —A type of cell without a true nucleus, such as a bacterium.

Retrovirus —A type of virus that inserts its genetic material into the chromosomes of the cells it infects.

Reverse transcriptase —The enzyme that allows a retrovirus to transcribe DNA from RNA.

Ribonucleic acid —RNA; the molecule translated from DNA in the nucleus that directs protein synthesis in the cytoplasm; it is also the genetic material of many viruses.

Rhabdoviruses are bullet-shaped, single-stranded RNA viruses. They are responsible for rabies, a fatal disease that affects dogs, rodents, and humans.

Retroviruses are unique viruses. They are double-stranded RNA viruses that contain an enzyme called reverse transcriptase. Within the host cell, the virus uses reverse transcriptase to make a DNA copy from its RNA genome. In all other organisms, RNA is synthesized from DNA. Cells infected with retroviruses are the only living things that reverse this process.

The first retroviruses discovered were viruses that infect chickens. The Rous sarcoma virus, discovered in the 1950s by Peyton Rous (1879–1970), was also the first virus that was linked to cancer. However, it was not until 1980 that the first human retrovirus was discovered. Called Human T-cell Leukemia Virus (HTLV), this virus causes a form of leukemia called adult T-cell leukemia. In 1983, another human retrovirus, Human Immunodeficiency Virus, the virus responsible for AIDS, was discovered independently by two researchers. Both HIV and HTLV are transmitted in body fluids.

Resources

BOOKS

Crawford, Dorothy. The Invisible Enemy: A Natural History of Viruses. New York: Oxford University Press USA, 2003.

Goyal, Sagar and Michael P. Doyle. Viruses in Foods. New York: Springer, 2006.

Hausler, Thomas. Viruses vs. Superbugs: A Solution to the Antibiotics Crisis? New York: MacMillan, 2006.

Sompayrac, Lauren. How Pathogenic Viruses Work. New York: Jones & Bartlett Publishers, 2002.

Kathleen Scogna

Virus

A virus is a program designed to infect and potentially damage files on a computer that receives it. The code for a virus is hidden within a file or program—such as a text document or a spreadsheet program—and when the file is opened or the program is launched, the virus inserts copies of itself, infecting the computer on which these files are opened. Because of this ability to reproduce itself, a virus can quickly spread to other programs, including the computer's operating system. A virus may reside on a computer system for some time before taking any action detectable to the user. Other viruses may cause trouble immediately. Some viruses cause little or no damage. For example, a virus may manifest itself as nothing more than a message that appears on the screen at certain intervals. Other viruses are much more destructive and can result in lost or corrupted files and data. Viruses may render a computer unusable, necessitating the reinstallation of the operating system and applications. Viruses can even be written to imbed some small miscalculation into, for example, a spreadsheet program. This sort of hidden problem may jeopardize the accuracy of all the work done with the infected program for a long time before it is even detected.

Viruses are written to target program files and macros, or a computer's boot sector, which is the portion of the hard drive that executes the steps necessary to start the hardware and software. Program viruses attach themselves to the executable files associated with software programs, and can then attack any file that is used to launch an application, usually files ending with the "exe" or "com" extensions. Macro viruses infect program templates that are used to create documents or spreadsheets. Once infected, every document or spreadsheet opened with the infected program becomes corrupted. Boot sector viruses attack the computer's hard drive and launch themselves each time the user boots, or starts, the computer. Viruses are often classified as Trojan Horses or Worms. A Trojan Horse virus is one that appears harmless on the surface but, in reality, destroys files or programs. A Worm attacks the computer's operating system and replicates itself again and again, until the system eventually crashes.

Another line of viruses is referred to as Malware, or, more generically as Spyware. These are viruses that are imbedded in files downloaded onto an unsuspecting computer while the user is browsing the Internet. Spyware programs, once on a computer, allow the creator of the virus to snoop on or monitor the infected computer's browser activities. A spyware virus usually implants "pop-up" ads that will appear on a user's screen periodically. These programs can down a computer, cause it to crash, and in some cases can even record for the sender the recipient's credit card numbers if it is used to purchase items while online. Spyware is usually a nuisance-level virus but in some cases can pose a more serious threat.

VIRUSES AND THE INTERNET

The Internet, with its global reach and rapid delivery times, provides the ideal breeding ground for viruses. Typically, someone who wants to spread a virus does so by sending out an e-mail message containing an infected attachment. The subject line on such a message sounds innocuous, so unsuspecting recipients open the message, unwittingly infecting their computers. More insidious yet, many viruses infect the recipient and then launch e-mail messages using the recipient's e-mail system address book and send themselves out to all of the recipient's list of colleagues, clients, vendors, friends, and family for whom an e-mail is found.

VIRUS PROTECTION

With new computer viruses appearing daily, keeping a computer or network of computers free of viruses is a daunting task. If, however, one views the proper use and maintenance of anti-virus software as a necessary part of running computers, the task becomes just another in the list of things one must do to maintain computers. The following are steps every computer user should follow to protect his or her computer from viruses.

1. Install an anti-virus software program to identify and remove viruses before they can cause any damage. These programs scan, or review, files that may come from floppy diskettes, the Internet, e-mail attachments, or networks, looking for patterns of code that match patterns in the anti-virus software vendor's database of known viruses. Once detected, the software isolates and removes the virus before it can be activated.
2. Update the anti-virus software weekly. Because the number of viruses is increasing all the time, it is important to keep anti-virus software up-to-date with information on newly identified viruses. Anti-virus software vendors are constantly updating their databases of information on viruses and making this information available to their customers via their Web sites or by e-mail.
3. Maintain a regular back-up procedure for all computers. This procedure may be as simple as keeping copies of important files on diskettes or CD-ROMs (in which case original software should be kept with these diskettes or CDs) and it may be as elaborate as a system designed to produce a mirror copy of a system, updating this copy every few minutes. For a small business, the most prudent level of back-up probably falls somewhere between these two extremes. Whatever the schedule is, it should include regular and periodic backing up of all computer systems and the remote storage of the backups' media in case of fire, flood, etc.
4. Do not open e-mail from unknown recipients or messages that contain unexpected attachments. A user should delete these types of messages. As a general rule, a user should scan every e-mail attachment for viruses before opening it—even an expected attachment—as the sender may have unknowingly sent an infected file.

NOTEWORTHY VIRUSES

One of the most costly and memorable viruses was the Love Bug virus of 2000. This virus targeted users of Microsoft's Outlook e-mail program. Originating in the Philippines, the subject line on the Love Bug message was the inviting "ILOVEYOU." If a user opened the attachment to this message, the virus quickly began to destroy files, targeting digital pictures and music files. The Love Bug virus also perpetuated itself by forwarding the original message to all e-mail addresses listed in the current recipient's Outlook address book. In this way, the virus was able to circle the globe in just two hours. The virus brought businesses to a standstill as companies, large and small, were forced to shut off incoming Internet e-mail messages and repair infected systems. In all, the Love Bug virus is estimated to have cost up to $10 billion in lost work hours.

Another record-setting virus, the fastest spreading e-mail worm ever, is MyDoom. This ominously named virus is a computer worm affecting Microsoft Windows. It was first sighted on January 2004 and was designed to send junk e-mail through infected computers. Early speculation about MyDoom held that the sole purpose of the worm was to perpetrate a distributed "denial-of-service attack" against the SCO Group. A denial of service attack is one in which a company Web site is flooded with e-mail causing it to overload, or shut down, and damaging any sales generated through the site, or services provided on the site.

Most viruses do not reach the level of fame that these two achieved, either because they are programmed to change as they spread, making them harder to identify and stop, or because they attack a niche sector of the computer-using market. Nonetheless, the damage that such viruses, even seemingly innocuous ones, can have on a company are great. Lost computer processing power equals slower-functioning computers, a lost of time and productivity. Lost files take time to retrieve from backup systems, assuming good backups exist. And rebuilding a computer that has been damaged by a virus is time-consuming for both the technician and the user.

Protection is the best way to save time, money, and the wear and tear that computer problems can have on all the people involved.

see also Internet Security

BIBLIOGRAPHY

"Attack of the Love Bug." Time. 15 May 2000.

Evers, Joris. "Computer Crime Costs $67 Billion, FBI Says." C/Net News.com . 20 January 2006.

Roberts, Paul. "Antivirus Companies Target Spyware, Worms." PC World. 25 August 2003.

Szor, Peter. The Art of Computer Virus Research and Defense. Addison-Wesley Professional, February 2005.

"The State of Internet Security." Symantec Corporation. Available from http://www.symantec.com/small_business/library/index.html. Retrieved on 13 April 2006.

                                Hillstrom, Northern Lights

                                 updated by Magee, ECDI

Virus

A virus is a parasite that must infect a living cell to reproduce. Although viruses share several features with living organisms, such as the presence of genetic material (DNA or RNA), they are not considered to be alive. Unlike cells, which contain all the structures needed for growth and reproduction, viruses are composed of only an outer coat (capsid), the genome, and, in some cases, a few enzymes. Together these make up the virion , or virus particle. Many illnesses in humans, including AIDS, influenza, Ebola fever, the common cold, and certain cancers, are caused by viruses. Viruses also exist that infect animals, plants, bacteria, and fungi.

Physical Description and Classification

Viruses are distinguished from free-living microbes, such as bacteria and fungi, by their small size and relatively simple structures. Diminutive viruses such as parvovirus may have a diameter of only 25 nanometers (nm, 10^-9 meters). Poxviruses, the largest known viruses, are about 300 nanometers across, just at the detection limits of the light microscope. Typical bacteria have diameters of 1,000 nanometers or more. Information on the structure of viruses has been obtained with several techniques, including electron

microscopy (EM). The limit of resolution of traditional EM is about 5 nm. With advanced EM techniques, such as cryogenic EM (cryoEM, in which the sample is rapidly frozen instead of exposed to chemical fixatives), coupled with computer image processing, smaller structures (1-2 nm) can be resolved. However, X-ray crystallography is the only method that allows for atomic-level resolution. Small viruses that produce uniform particles can be crystallized. The first atomic-level structure of a virus, tomato bushy stunt virus, was solved in 1978.

There is great diversity among viruses, but a limited number of basic designs. Capsids are structures that contain the viral genomes; many have icosahedral symmetry. An icosahedron is a three-dimensional, closed shape composed of twenty equilateral triangles. Viral proteins, in complexes termed "capsomers," form the surface of the icosahedron.

Other viruses, such as the virus that causes rabies, are helical (rod shaped). The length of helical viruses can depend on the length of the genome, the DNA or RNA within, since there are often regular structural interactions between the nucleic acids of the genome and the proteins that cover it.

A lipid -containing envelope is a common feature of animal viruses, but uncommon in plant viruses. Embedded in the envelope are surface proteins, usually glycoproteins that help the virus interact with the surface of the cell it is infecting. A matrix layer of proteins often forms a bridge between the surface glycoproteins and the capsid. Some viruses, such as the picornaviruses, are not enveloped, nor do they have a matrix layer. In these viruses, cell-surface interactions are mediated by the capsid proteins.

Some viruses have compound structures. The head of the T4 bacterial virus (bacteriophage) is icosahedral and is attached via a collar to a contractile

tail with helical symmetry. Large viruses, such as the herpesviruses and poxviruses, can have higher-ordered and more complex structures.

Classification of viruses considers the genome characteristics, virion shape and macromolecular composition, and other properties, such as antigenicity and host range. A scheme for classification of viruses based on the type of nucleic acid (DNA or RNA) present in the virus particle and the method of genome replication was devised by David Baltimore, co-discoverer of reverse transcriptase (see Table 1). Reverse transcriptase is an enzyme that converts retroviral genomic single-stranded (ss) RNA into doubled-stranded (ds) DNA.

Viral genomes can be RNA or DNA, positive or negative in polarity, ss or ds, and one continuous (sometimes circular) molecule or divided into segments. By convention, messenger RNA (mRNA) that can be directly translated to protein is considered positive sense (or positive in polarity). DNA with a corresponding sequence (that is, the coding strand of double-stranded DNA) is also a positive-sense strand. An RNA or DNA molecule with the reverse complementary sequence to mRNA is a negative-sense strand. A few viruses have been identified that contain one or more "ambisense" genomic RNA segments that are positive sense in one part of the molecule (this part can be translated directly into protein) and negative sense (reverse complement of coding sequence) in the rest of the molecule.

Virus Replication Cycle

For a virus to multiply it must infect a living cell. All viruses employ a common set of steps in their replication cycle. These steps are: attachment, penetration, uncoating, replication, assembly, maturation, and release.

Attachment and Penetration.

A virion surface protein must bind to one or more components of the cell surface, the viral receptors. The presence or absence of receptors generally determines the type of cell in which a virus is able to replicate. This is called viral tropism. For example, the poliovirus receptor is present only on cells of higher primates and then in a limited subset of these, such as intestine and brain cells. While called virus receptors, these are actually used by the cell for its own purposes, but are exploited by the virus for entry.

Entry of the viral genome into the cell can occur by direct penetration of the virion at the cell surface or by a process called endocytosis, which is the engulfment of the particle into a membrane-based vesicle. If the latter, the virus is released when the vesicle is acidified inside the cell. Enveloped viruses may also fuse with the cellular surface membrane, which results in release of the capsid into the cytoplasm . Surface proteins of several viruses contain "fusion peptides," which are capable of interacting with the lipid bilayers of the host cell.

Uncoating and Replication.

After penetration, viral capsid proteins must be removed, at least partly, to express and replicate the viral genome. In the case of most DNA viruses, the capsid is routed to the nucleus prior to uncoating. An example can be seen in the poxviruses, whose large DNA genomes encode most of the proteins needed for DNA replication. These viruses uncoat and replicate completely in the cytoplasm. RNA viruses typically lose the protective envelope and capsid proteins upon penetration into the cytoplasm. In reoviruses, only an outer protein shell is removed and replication takes place inside a structured subviral particle.

Viral genomes must be expressed as mRNAs in order to be translated into structural proteins for the capsids and, in some cases, as replicative proteins for replicating the virus genome. Viral genomes must also provide templates that can be replicated to produce progeny genomes that will be packaged into newly produced virions. Replication details vary among the different types of viruses.

The ss positive-sense DNA of parvoviruses is copied by host DNA polymerase (the enzyme that replicates DNA) in the nucleus into a negative-sense DNA strand. This in turn serves as a template for mRNA and progeny DNA synthesis. The genomes of larger DNA viruses, with the exception of the poxviruses, are also transcribed and replicated in the nucleus by a combination of viral and host enzymes (for example, DNA-dependent RNA polymerses for transcription of mRNAs, DNA-dependent DNA polymerase for genome replication).

Positive-polarity RNA virus genomes can be translated directly, but for effective progeny production additional rounds of RNA replication via a negative-stranded intermediate are required. This is accomplished by a viral transcriptase (RNA-dependent RNA polymerase) and associated cofactors. Single-stranded negative-sense RNA viruses of animals must also carry a viral transcriptase to transcribe functional mRNAs and subsequently produce proteins, since this RNA-to-RNA enzymatic activity is typically lacking in animal cells.

Retroviruses are unique among viruses in that the genome is diploid, meaning that two copies of the positive-polarity RNA genome are in each virus particle. The genomic RNA is not translated into protein, but rather serves as a template for reverse transcription, which produces a double-stranded DNA via a viral reverse transcription enzyme. The DNA is subsequently integrated into the host cell chromosomal DNA. Hepadnaviruses also encode a reverse transcriptase, but replication occurs inside the virus particle producing the particle-associated genomic DNA.

Assembly, Maturation, and Release.

As viral proteins and nucleic acids accumulate in the cell, they begin a process of self-assembly. Viral self-assembly was first demonstrated in a seminal series of experiments in 1955, wherein infectious particles of tobacco mosaic virus spontaneously formed when purified coat protein and genomic RNA were mixed. Likewise, poliovirus capsomers are known to self-assemble to form a procapsid in the cytoplasm. Progeny positive-strand poliovirus RNAs then enter this nascent particle. "Chaperone" proteins (chaparonins) of the cell play a critical role in facilitating the assembly of some viruses. Their normal role is to help fold cellular proteins after synthesis.

The maturation and release stages of the replication cycle may occur simultaneously with the previous step, or may follow in either order. Many viruses assemble their various components into "immature" particles. Further intracellular or extracellular processing is required to produce a mature infectious particle. This may involve cleavage of precursors to the structural proteins, as in the case of retroviruses.

Viruses that are not enveloped usually depend upon disintegration or lysis of the cell for release. Enveloped viruses can be released from the cell by the process of budding. In this process the viral capsid and usually a matrix layer are directed to a modified patch of cellular membrane. Interactions between the matrix proteins and/or envelope proteins drive envelopment. In the case of viruses that bud at the cell surface, such as some togaviruses and retroviruses (including HIV), this also results in release of the virus particles. If the virus acquires a patch of the nuclear membrane (as is the case with herpesviruses), then additional steps involving vesicular transport may be required for the virus to exit the cell.

Infection Outcomes

Viral infection can result in several different outcomes for the virus and the cell. Productive infection, such that each of the seven steps outlined above occurs, results in the formation of progeny viruses. Cells productively infected with poliovirus can yield up to 100,000 progeny virions per cell, although only a small fraction (fewer than 1 per 1,000) of these are capable of going on to carry out a complete replication cycle of their own. Productive infection may induce cell lysis, which results in the death of the cell. Nonenveloped viruses typically induce cell lysis to permit release of progeny virions. Many enveloped viruses also initiate events that result in cell death by various means, including apoptosis , necrosis , or lysis.

Viral infection may be abortive, in which one or more necessary factors, either viral or cellular, are absent and progeny virions are not made. Infection may be nonproductive, at least transiently, but viral genomes may still become resident in the host cell. Herpesviruses and retroviruses can establish latent infections. Latently infected cells may express a limited number of viral products, including those that result in cell transformation. Latent infections can often be activated by various stimuli, such as stress in the case of herpesviruses, to undergo a productive infection.

Viral Cancers

Infection with certain viruses can also result in cell transformation, stable genetic changes in the cell that result in disregulated cell growth and extended growth potential (immortalization). In animals, such virally induced cellular changes can result in cancer. This correlation was first made by Harry Rubin and Howard Temin in the 1950s, when they observed that Rous sarcoma virus, a retrovirus capable of inducing solid tumors in chickens, could also cause biochemical and structural changes and extend the proliferative potential of cultured chicken cells.

Viruses are perhaps second only to tobacco as risk factors for human cancers. DNA tumor viruses include papillomaviruses and various herpes viruses (such as HHV-8, which causes Kaposi's sarcoma ). More than sixty strains of human papillomaviruses (HPV) have been identified. HPV cause warts, which are benign tumors, but are also the causes of malignant penile, vulval, and cervical cancers. Infection with hepatitis B or C viruses is associated with increased incidence of liver cancer. Adenoviruses have been shown to induce cancers in animals, but not in humans. Retroviruses can also cause cancer in various animal species, including humans. HTLV-1 causes adult T-cell leukemia in about 1 percent of infected humans.

Viruses can cause cancer through their effects on two important cellular genes or gene products: tumor suppressors and oncogenes . These genes are critical players in cell-cycle regulation. One protein product from HPV binds to the retinoblastoma (Rb) tumor suppressor protein. HPV E6 protein binds p53 tumor suppressor protein and promotes its degradation. Acutely transforming retroviruses, which induce tumors in a short time period of weeks to months, carry modified versions of cellular oncogenes, called viral oncogenes. Slowly transforming retroviruses also subvert cellular oncogenes, but by integrating into or near the oncogene, thereby altering its expression, a process that can take years because of the apparently random nature of retrovirus integration.

Vaccines

Many viral infections can be prevented by vaccination. Several classes of vaccines are currently in use in humans and animals. Inactivated vaccines, such as the poliovirus vaccine developed by Jonas Salk, are produced from virulent viruses that are subjected to chemical treatments that result in loss of infectivity without complete loss of antigenicity (antigenicity is the ability to produce immunity). Another approach is the use of weakened variants of a virus with reduced pathogenicity to induce a protective immune response without disease. While vaccines are usually given before exposure to a virus, postexposure vaccines can cure some virus infections with extended incubation periods, such as rabies.

Vaccines against smallpox eradicated the illness in 1980. It is believed that it may also be possible to eliminate polio. A recombinant vaccine against hepatitis B virus is now produced in yeast. However, developing effective vaccines to some viruses, including the common cold viruses, HIV-1, herpesviruses, and HPV, is proving very difficult principally due to the existence of many variants. Public health measures, such as mosquito control programs to curb the spread of viral diseases transmitted by these vectors , and safe-sex campaigns to slow the spread of sexually transmitted diseases, can also be effective. Because viruses replicate in cells, drugs that target viruses typically also affect cell functions. These therapeutic agents must be active against the virus while having "acceptable toxicity" to the host organism. The majority of the specific antiviral drugs currently in use target viral enzymes. For example, nucleoside analogues that target viral polymerases are active against HIV and certain herpesviruses.

see also Biotechnology; Cancer; Cell, Eukaryotic; DNA Polymerases; Gene Therapy; HIV; Oncogenes; Retrovirus; Transformation; Tumor Suppressor Genes; Viroids and Virusoids.

Robert F. Garry

Bibliography

Garrett, Laurie. The Coming Plague: Newly Emerging Diseases in a World out of Balance. New York: Penguin Books, 1994.

Kolata, Gina B. Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus That Caused It. New York: Farrar, Straus and Giroux, 1999.

Preston, Richard. The Hot Zone. New York: Random House, 1994.

Internet Resource

Sanders, David M., and Robert F. Garry. "All the Virology on the World Wide Web." <www.virology.net>.

Virus

A virus is a small, infectious agent that is made up of a core of genetic material surrounded by a shell of protein. The genetic material (which is responsible for carrying forward hereditary traits from parent cells to offspring) may be either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). Viruses are at the borderline between living and nonliving matter. When they infect a host cell, they are able to carry on many life functions, such as metabolism and reproduction. But outside a host cell, they are as inactive as a grain of sand.

Viruses cause disease by infecting a host cell and taking over its biochemical functions. In order to produce new copies of itself, a virus must use the host cell's reproductive "machinery." The newly made viruses then leave the host cell, sometimes killing it in the process, and proceed to infect other cells within the organism.

Viruses can infect plants, bacteria, and animals. The tobacco mosaic virus, one of the most studied of all viruses, infects tobacco plants. Animal viruses cause a variety of diseases, including AIDS (acquired immuno deficiency syndrome), hepatitis, chicken pox, smallpox, polio, measles, rabies, the common cold, and some forms of cancer.

Viruses that affect bacteria are called bacteriophages, or simply phages (pronounced FAY-jez). Phages are of special importance because

Words to Know

Adult T cell leukemia (ATL): A form of cancer caused by the retro-virus HTLV.

AIDS (acquired immunodeficiency syndrome): A set of life-threatening, opportunistic infections that strike people who are infected with the retrovirus HIV.

Bacteriophage: A virus that infects bacteria.

Capsid: The outer protein coat of a virus.

DNA (deoxyribonucleic acid): Genetic material consisting of a pair of nucleic acid molecules intertwined with each other.

Envelope: The outermost covering of some viruses.

Gene: Unit of heredity contained in the nucleus of cells that is composed of DNA and that carries information for a specific trait.

Host cell: The specific cell that a virus targets and infects.

HIV (human immunodeficiency virus): The retrovirus that causes AIDS.

Human T cell leukemia virus (HTLV): The retrovirus that causes ATL.

Infectious: Relating to a disease that is spread primarily through contact with someone who already has the disease.

Lysogenic cycle: A viral replication cycle in which the virus does not destroy the host cell but coexists within it.

Lytic cycle: A viral replication cycle in which the virus destroys the host cell.

Metabolism: The sum of all the physiological processes by which an organism maintains life.

Orthomyxovirus: Group of viruses that causes influenza in humans and animals.

Proteins: Complex chemical compounds that are essential to the structure and functioning of all living cells.

Retrovirus: A type of virus that contains a pair of single stranded RNA molecules joined to each other.

Reverse transcriptase: An enzyme that makes it possible for a retro-virus to produce DNA from RNA.

Ribonucleic acid (RNA): Genetic material consisting of a single strand of nucleic acid.

they have been studied much more thoroughly than have viruses. In fact, much of what we now know about viruses is based on the study of phages. Although there are both structural and functional differences between the two, they share many characteristics in common.

Structure of viruses

Although viral structure varies considerably among different types of viruses, all viruses share some common characteristics. All viruses contain either RNA or DNA surrounded by a protective protein shell called a capsid. The genetic material in a virus may take one of four forms: a double strand of DNA, a single strand of DNA, a double strand of RNA, or a single strand of RNA. The size of the genetic material of viruses is often quite small. Compared to the 100,000 genes that exist within human DNA, viral genes number from 10 to about 200 genes.

Viruses exist in one of three forms, as shown in Figure 1. They are named on the basis of their general shape as rodlike, icosahedral (having 20 sides), or spherical. Some viruses also have an outer covering known as an envelope that surrounds the capsid. The outer surface of some kinds of viral particles contain threadlike "spikes" that are often used in helping a virus invade a host cell (for example, the spherical virus in Figure 1).

Viral infection

A virus remains totally inactive until it attaches itself to and infects a host cell. Once that happens, the virus may follow one of two paths. First, the virus may insert its genetic material (it is always DNA in this case) into the DNA of the host cell. The combined host-viral DNA is then

carried along in the host cell as it lives and reproduces, generation after generation. Viruses that follow this pathway are said to be temperate or lysogenic viruses. At some point in the host cell's life, the viral DNA may be extracted (taken out) from the host DNA and follow the second pathway.

The second pathway available to viruses is called the lytic cycle. In the lytic cycle, the virus first attaches itself to the surface of the host cell. It then makes a hole in the cell membrane and injects its genetic material (DNA or RNA). The viral capsid is left behind outside the cell.

The next step depends on the nature of the viral genetic material, whether that material is single stranded or double stranded DNA or RNA. The end result of any one of the processes is that many additional copies of the viral capsid and the viral genetic material are made. These capsids and genetic material are then assembled into new viral particles. The single collection of genetic material originally injected into the host cell has been used to make dozens or hundreds of new viral particles.

When these particles have been assembled, they burst through the cell membrane. In the act, the host cell is destroyed. The new viral particles are then free to find other host cells and to repeat the process.

Retroviruses

Retroviruses make up an unusual group of viruses. Their genetic material consists of two single strands of RNA linked to each other. Retroviruses also contain an essential enzyme known as reverse transcriptase.

The unusual character of retroviruses is that they have evolved a method for manufacturing protein beginning with RNA. In nearly all living organisms, the pattern by which protein is manufactured is as follows: DNA in the cell's nucleus carries directions for the production of new protein. The coded message in DNA molecules is copied into RNA molecules. These RNA molecules then direct the manufacture of new protein. In retroviruses, that process is reversed: viral RNA is used to make new viral DNA. The viral DNA is then incorporated into host cell DNA, where it is used to direct the manufacture of new viral protein.

The first retrovirus discovered was the Rous sarcoma virus (RSV) that infects chickens. It was named after its discoverer, the American pathologist Peyton Rous (1879–1970). Other animal retroviruses are the simian immunodeficiency virus (SIV), which attacks monkeys, and the feline leukemia virus (FELV), which causes feline leukemia in cats. The first human retrovirus was discovered in 1980 by a research team headed by American virologist Robert Gallo (1937– ). Called human T cell leukemia virus (HTLV), this virus causes a form of leukemia (cancer of the blood) called adult T cell leukemia. In 1983–84, another human retro-virus was discovered. This virus, the human immunodeficiency virus (HIV), is responsible for AIDS.

The common cold and influenza

Two of the most common viral diseases known to humans are the common cold and influenza. The common cold, also called acute coryza or upper respiratory infection, is caused by any one of some 200 different viruses, including rhinoviruses, adenoviruses, influenza viruses, para-influenza viruses, syncytial viruses, echoviruses, and coxsackie viruses. Each virus has its own characteristics, including its favored method of transmission and its own gestation (developmental) period. All have been implicated as the agent that causes the runny nose, cough, sore throat, and sneezing that advertise the presence of the common cold. According to experts, more than a half billion colds strike Americans every year, an average of two infections for each man, woman, and child in the United States. In spite of intense efforts on the part of researchers, there are no cures, no preventative treatments, and very few treatments for the common cure.

Viruses that cause the common cold can be transmitted from one person to another by sneezing on the person, shaking hands, or handling an object previously touched by the infected person. Oddly, direct contact with an infected person, as in kissing, is not an efficient way for the virus to spread. In only about 10 percent of contacts between an infected and uninfected person does the latter get the virus.

Contrary to general opinion, walking around in a cold rain will not necessarily cause a cold. Viruses like warm, moist surroundings, so they thrive indoors in the winter. However, being outdoors in cold weather can dehydrate the mucous membranes in the nose and make them more susceptible to infection by a rhinovirus. The viruses that cause colds mutate with regularity. Each time a virus is passed from one person to the next, it may change slightly, so it may not be the virus the first person had.

The common cold differs in several ways from influenza, commonly known as the flu. Cold symptoms develop gradually and are relatively mild. The flu has a sudden onset and has more serious symptoms that usually put the sufferer to bed. The flu lasts about twice as long as the cold. Also, influenza can be fatal, especially to elderly persons. Finally, the number of influenza viruses is more limited than the number of cold viruses, and vaccines are available against certain types of flu.

Influenza. Influenza is a highly contagious illness caused by a group of viruses called the orthomyxoviruses. Infection with these viruses leads to an illness usually characterized by fever, muscle aches, fatigue (tiredness), and upper respiratory obstruction and inflammation. Children and young adults usually recover from influenza within 3 to 7 days with no complications. However, influenza can be a very serious disease among older adults, especially those over 65 with preexisting conditions such as heart disease or lung illnesses. Most hospitalizations and deaths from influenza occur in this age group. Although an influenza vaccine is available,

it does not offer complete protection against the disease. The vaccine has been shown only to limit the complications that may occur due to influenza.

Three types of orthomyxoviruses cause illness in humans and animals: types A, B, and C. Type A causes epidemic influenza, in which large numbers of people become infected during a short period of time. Flu epidemics caused by Type A orthomyxoviruses include the worldwide outbreaks of 1918, 1957, 1968, and 1977. Type A viruses infect both humans and animals and usually originate in Asia, where a large population of ducks and swine incubate the virus and pass it to humans. (Incubate means to provide a suitable environment for growth, in this case within the animals' bodies.) Asia also has a very large human population that provides a fertile ground for viral replication.

Type B influenza viruses are not as common as type A viruses. Type B viruses cause outbreaks of influenza about every two to four years. Type C viruses are the least common type of influenza virus and cause irregular and milder infections.

An important characteristic of all three kinds of influenza viruses is that they frequently mutate. Because they contain only a small amount of genetic material, flu viruses mutate frequently. The result of this frequent mutation is that each flu virus is different, and people who have become immune to one flu virus are not immune to other flu viruses. The ability to mutate frequently, therefore, allows these viruses to cause frequent outbreaks.

The most common complication of influenza is pneumonia, a disease of the lungs. Pneumonia may be viral or bacterial. The viral form of pneumonia that occurs with influenza can be very severe. This form of pneumonia has a high mortality rate. Bacterial pneumonia may develop when bacteria accumulate in the lungs. This type of pneumonia occurs five to ten days after onset of the flu. Because it is bacterial in origin, it can be treated with antibiotics.

Flu is treated with rest and fluids. Maintaining a high fluid intake is important, because fluids increase the flow of respiratory secretions, which may prevent pneumonia. A new antiviral medication is prescribed for people who have initial symptoms of the flu and who are at high risk for complications. This medication does not prevent the illness, but reduces its duration and severity.

A flu vaccine is available that is formulated each year against the current type and strain of flu virus. The vaccine would be most effective in reducing attack rates if it were effective in preventing influenza in schoolchildren. However, in vaccine trials, the vaccine has not been shown to be effective in flu prevention in this age group. In certain populations, particularly the elderly, the vaccine is effective in preventing serious complications of influenza and thus lowers mortality.

[See also AIDS (acquired immunodeficiency syndrome); Cancer; Disease; Immune system; Nucleic acid; Poliomyelitis; Vaccine ]