Efficient Vpu-Mediated Tetherin Antagonism by an HIV-1 Group O Strain.

摘要: Simian immunodeficiency viruses (SIVs) use their Nef proteins to counteract the restriction factor tetherin. However, a deletion in human tetherin prevents antagonism by of SIVcpz and SIVgor, which represent ape precursors virus type 1 (HIV-1). To promote release from infected cells, pandemic HIV-1 group M strains evolved Vpu as antagonist, while protein less widespread O acquired ability target region adjacent this deletion. In study, we identified an unusual strain (RBF206) that effective antagonist While both RBF206 exert anti-tetherin activity transient-transfection assays, mainly promotes CD4+ T cells. Although mutations distinct adaptive changes observed Vpus (M-Vpus) were critical for acquisition its activity, O-Vpu potently suppresses NF-κB activation reduces CD4 cell surface expression. Interestingly, counteracts largely species-independent manner, degrading long short isoforms Downmodulation CD4, but not counteraction tetherin, was dependent on cellular ubiquitin ligase machinery. Our data present first example efficiently antagonizes suggest O-Nefs may be suboptimal.IMPORTANCE Previous studies showed groups two alternative strategies ortholog switched due cytoplasmic domain O, lacks Vpu-mediated is able Here report exception, identifying whose are those found M-Vpus mediate efficient factor. results further illustrate enormous flexibility counteracting defense mechanisms.