Human Cytomegalovirus Inhibits IFN-α-Stimulated Antiviral and Immunoregulatory Responses by Blocking Multiple Levels of IFN-α Signal Transduction

作者: B. M. Rahill , Yingxue Zhang , D. D. Sedmak , D. M. Miller , W. J. Waldman

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摘要: The type I IFNs represent a primordial, tightly regulated defense system against acute viral infection. IFN-α confers resistance to infection by activating conserved signal transduction pathway that up-regulates direct antiviral effectors and induces immunomodulatory activities. Given the critical role of in anti-human cytomegalovirus (HCMV) immunity profound ability HCMV escape host immune response, we hypothesized blocks IFN-α-stimulated responses disrupting multiple levels pathway. We demonstrate inhibits MHC class I, IFN regulatory factor-1, MxA 2′,5-oligoadenylate synthetase gene expression, transcription factor activation, signaling infected fibroblasts endothelial cells decreasing expression Janus kinase 1 p48, two essential components This investigation is first report inhibition herpesvirus. propose this novel mechanism major means which capable escaping establishing persistence.

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