Rotavirus Antagonism of the Innate Immune Response 英文参考文献.docVIP

Viruses 2009, 1, 1035-1056; doi:10.3390/v1031035 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Rotavirus Antagonism of the Innate Immune Response Michelle M. Arnold and John T. Patton * Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive MSC 8026, Room 6314, Bethesda, MD 20892-8026, USA; E-Mail: arnoldm@ * Author to whom correspondence should be addressed; E-Mail: jpatton@; Tel.: +1-301-594-1615; Fax: +1-301-496-8312. Received: 14 September 2009; in revised form: 5 November 2009 / Accepted: 20 November 2009 / Published: 24 November 2009 Abstract: Rotavirus is a primary cause of severe dehydrating gastroenteritis in infants and young children. The virus is sensitive to the antiviral effects triggered by the interferon (IFN)-signaling pathway, an important component of the host cell innate immune response. To counteract these effects, rotavirus encodes a nonstructural protein (NSP1) that induces the degradation of proteins involved in regulating IFN expression, such as members of the IFN regulatory factor (IRF) family. In some instances, NSP1 also subverts IFN expression by causing the degradation of a component of the E3 ubiquitin ligase complex responsible for activating NF-?B. By antagonizing multiple components of the IFN-induction pathway, NSP1 aids viral spread and contributes to rotavirus pathogenesis. Keywords: rotavirus; NSP1; interferon regulatory factor; IRF 1. Introduction The innate immune system provides an immediate mechanism of suppressing the replication and spread of viruses. The production of type I interferon (IFN), including IFN-? and IFN-? subtypes, is critical to an effective innate immune response. Type I IFNs activate the expression of hundreds of IFN-stimulated genes (ISGs), which play critical roles not only in the innate immune response, but also in B-cell and T-cell activation, cell cycle regulation,