title: Rotavirus and reovirus modulation of the interferon response.
abstract: The mammalian reoviruses and rotaviruses have evolved specific mechanisms to evade the Type I interferon (IFN) antiviral response. Rotavirus likely represses the IFN response by at least 4 mechanisms. First, the rotavirus protein NSP1, most likely functioning as an E3 ligase, can induce proteasome-dependent degradation of the transcription factors IRF3, IRF5, and IRF7 to prevent their induction of IFN. Second, NSP1 can induce proteasome-dependent degradation of the ubiquitin ligase complex protein beta-TrCP, resulting in stabilization of I kappaB and concomitant failure of virus to activate NF-kappaB for induction of IFN. Third, rotavirus may sequester NF-kappaB in viroplasms. And fourth, rotavirus can prevent STAT1 and STAT2 nuclear translocation. The predominant mechanism for rotavirus inhibition of the IFN response is likely both rotavirus strain-specific and cell type-specific. The mammalian reoviruses also display strain-specific differences in their modulation of the IFN response. Reovirus activates RIG-I and IPS-1 for phosphorylation of IRF3. Reovirus-induced activation of MDA5 also participates in induction if IFN-beta, perhaps through activation of NF-kappaB. Reovirus likely inhibits the IFN response by at least 3 virus strain-specific mechanisms. First, the reovirus mu2 protein can induce an unusual nuclear accumulation of IRF9 and repress IFN-stimulated gene (ISG) expression, most likely by disrupting IRF9 function as part of the heterotrimeric transcription factor complex, ISGF3. Second, the reovirus sigma 3 protein can bind dsRNA and prevent activation of the latent antiviral effector protein PKR. And third, genetic approaches have identified the reovirus lambda 2 and sigma 2 proteins in virus strain-specific modulation of the IFN response, but the significance remains unclear. In sum, members of the family Reoviridae have evolved a variety of mechanisms to subvert the host's innate protective response.
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA. barbara_sherry@ncsu.edu
authors.forename: Barbara
authors.initials: B
authors.lastname: Sherry
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D006801:Humans; D050835:Interferon Regulatory Factors / Q000276:immunology / Q000378:metabolism; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050832:Interferon-Stimulated Gene Factor 3 / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D020365:RNA Helicases / Q000276:immunology / Q000378:metabolism; D012401:Rotavirus / Q000276:immunology* / Q000472:pathogenicity; D012400:Rotavirus Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D017361:Viral Nonstructural Proteins / Q000276:immunology / Q000378:metabolism*; D014774:Virulence
chemical_list: D050835:Interferon Regulatory Factors; D007370:Interferon Type I; D050832:Interferon-Stimulated Gene Factor 3; D016328:NF-kappa B; D050791:STAT Transcription Factors; D017361:Viral Nonstructural Proteins; C104282:nsp1 protein, Rotavirus; D020365:RNA Helicases
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