The enhanced production of the cytokines called interferons is one of the body's earliest responses to a viral infection. These endogenous proteins exert potent antiviral, immunoregulatory, and antiproliferative effects and are classified according to the cell type from which they were initially derived. Interferon-a (type I, leukocyte) and interferon p-p (type I, fibroblast) are synthesized by most types of cells in response to viral infection, certain cytokines, and double-stranded RNA. Interferon-y (type II, immune) is produced by natural killer (NK) cells and T lymphocytes in response to antigens, mitogens, and certain cytokines. Interferon-a and interferon-p exert the most potent antiviral effects; interferon-y is antiviral and strongly immunomodulatory.
Although interferons do not directly interact with viral particles, they exert a complex range of effects on virus-infected cells that result in the inhibition of viral penetration, uncoating, mRNA synthesis, translation, and/or virion assembly and release. Interferons bind to cell surface receptors and initiate the JAK-STAT signal transduction pathway. This leads to the induction of numerous proteins, including 2'-5'-oligoadenylate synthetase (2'-5'OAS) and interferon-induced protein kinase. 2'-5'OAS initiates the activation of a cellular ribonuclease that cleaves single-stranded RNAs, and interferon-induced protein kinase phosphorylates and inactivates an elongation factor (eIF-2) involved in translation. Interferons also induce the production of inflammatory cytokines and biological oxidants that further enhance the host immune response. Viral families differ with respect to the step or steps at which interferons exert their effects. Certain viruses are resistant to interferons because they produce proteins that counteract interferon's effects.
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