Interferons

Interferons are members of a larger class of proteins called cytokines (proteins that carry signals between cells). Most interferons are classified as alpha, beta, or gamma interferons, depending on their molecular structure. Two other classes of interferons—omega and tau—have also been discovered. So far, more than 20 different kinds of interferon-alpha have been discovered but only beta and one gamma interferon have been identified.

Interferons are differentiated primarily through their amino acid sequence. (Amino acids are molecular chains that make up proteins.) Interferon-alpha, -beta, -tau, and -omega, which have relatively similar amino acid sequences, are classified as type I interferons. Type I interferons are known primarily for their ability to make cells resistant to viral infections. Interferongamma is the only type II interferon, classified as such because of its unique amino acid sequence. This interferon is known for its ability to regulate overall immune system functioning.

In addition to their structural makeup, type I and type II interferons have other differences. Type I interferons are produced by almost every cell in the body while the type II interferon-gamma is produced only by specialized cells in the immune system known as T lymphocytes and natural killer cells. The two classes also bind to different kinds of receptors, which lie on the surface of cells and attract and combine with specific molecules of various substances.

Interferons work to stop a disease when they are released into the blood stream and then bind to cell receptors. After binding, they are drawn inside the cell's cytoplasm, where they cause a series of reactions that produce other proteins that fight off disease. Scientists have identified over 30 disease fighting proteins produced by interferons.

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 alpha-interferon (macrophage interferon), as well as a single gene for beta-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. Alpha- and beta-interferons are structurally related glycoproteins of 166 and 169 amino acid residues. In contrast, gamma-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 alpha-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 synthestase). In the presence of double-stranded RNA, this enzyme catalyses the polymerisation 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.