How Does Vaccinia Virus Interfere With Interferon?

Abstract

Interferons (IFNs) are secreted glycoproteins that are produced by cells in response to virus infection and other stimuli and induce an antiviral state in cells bearing IFN receptors. In this way, IFNs restrict virus replication and spread before an adaptive immune response is developed. Viruses are very sensitive to the effects of IFNs and consequently have evolved many strategies to interfere with interferon. This is particularly well illustrated by poxviruses, which have large dsDNA genomes and encode hundreds of proteins. Vaccinia virus is the prototypic poxvirus and expresses many proteins that interfere with IFN and are considered in this review. These proteins act either inside or outside the cell and within the cytoplasm or nucleus. They function by restricting the production of IFN by blocking the signaling pathways leading to transcription of IFN genes, stopping IFNs binding to their receptors, blocking IFN-induced signal transduction leading to expression of interferon-stimulated genes (ISGs), or inhibiting the antiviral activity of ISG products.

Keywords: AP-1; GAS; IRF3; ISRE; Innate immunity; Interferon; Interferon alpha/beta; Interferon gamma; Interferon lambdas; Interferon receptors; Interferon-inducible genes; JAK–Stat; NF-κB; Signaling pathways; Smallpox; Vaccine; Vaccinia virus.