Vaccinia virus protein N2 is a nuclear IRF3 inhibitor that promotes virulence
作者： Brian J. Ferguson , Camilla T. O. Benfield , Hongwei Ren , Vivian H. Lee , Gordon L. Frazer
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摘要: Vaccinia virus (VACV) expresses many proteins that are non-essential for replication but promote virulence by inhibiting components of the host immune response to infection. These immunomodulators include a family have, or predicted structure related B-cell lymphoma (Bcl)-2 protein. Five members VACV Bcl-2 (N1, B14, A52, F1 and K7) have had their crystal solved, others been characterized function assigned (C6, A46), be uncharacterized hitherto (N2, B22, C1). Data presented here show N2 is nuclear protein expressed early during infection inhibits activation interferon regulatory factor (IRF)3. Consistent with its localization, IRF3 downstream TANK-binding kinase (TBK)-1 after translocation into nucleus. A mutant strain Western Reserve lacking N2L gene (vΔN2) showed normal spread in cultured cells compared wild-type parental (vN2) revertant (vN2-rev) viruses, was attenuated two murine models After intranasal infection, vΔN2 induced lower weight loss signs illness, cleared more rapidly from infected tissue. In intradermal model smaller lesions were resolved rapidly. summary, an intracellular activity
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