Interferon actions

Interferons are species-specific proteins, which induce antiviral and antiproliferative responses in animal cells. They are a major defense against viral infections and abnormal growths (neoplasms). Interferons are produced in response to penetration of animal cells by viral (or synthetic) nucleic acid and then leave the infected cell to confer resistance on other cells of the organism. In contrast to antibodies, interferons are not virus specific but host specific. Thus, viral infections of human cells are inhibited only by human interferon. The human genome contains 14 nonallelic and 9 allelic genes of α-interferon (macrophage interferon), as well as a single gene for β-interferon (fibroblast interferon). Genes for any two or more variants of interferon, which have originated from the same wild-type gene are called allelic genes and will occupy the same chromosomal location (locus). Variants originating from different standard genes are termed non allelic. α- and β-interferons are structurally related glycoproteins of 166 and 169 amino acid residues. In contrast, γ-interferon (also known as immune interferon) is not closely related to the other two and is not induced by virus infection. It is produced by T-cells after stimulation with the cytokine interleukin-2. It enhances the cytotoxic activity of T-cells, macrophages and natural killer cells and thus has antiproliferative effects. It also increases the production of antibodies in response to antigens administered simultaneously with α-interferon, possible by enhancing the antigen-presenting function of macrophages.

Interferons bind to specific receptors on the cell surface, and induce a signal in the cell interior. Two induction mechanisms have been elucidated. One mechanism involves the induction of protein kinase by interferon, which, in the presence of double-stranded RNA , phosphorylates one subunit of an initiation factor of protein synthesis (eIF-2B), causing the factor to be inactivated by sequestration in a complex. The second mechanism involves the induction of the enzyme 2',5'-oligoadenylate synthetase (2',5'-oligo A synthetase). In the presence of double-stranded RNA, this enzyme catalyses the polymerization of ATP into oligomers of 2 to 15 adenosine monophosphate residues which are linked by phosphodiester bonds between the position 2' of one ribose and 5' of the next. These 2',5'-oligoadenylates activate an interferon specific RNAase, a latent endonuclease known as RNAase L which is always present but not normally active. RNAase cleaves both viral and cellular single stranded mRNA. Interferons therefore do not directly protect cells against viral infection, but rather render cells less suitable as an environment for viral replication. This condition is known as the antiviral state.

See also Antibody and antigen; Immune system; Immunology; Viruses and responses to viral infection