Tetherin Antagonism by HIV-1 Group M Nef Proteins

Juan Arias, Marta Colomer-Lluch, Benjamin von Bredow, Justin Greene, Julie MacDonald, David O'Connor, Ruth Serra Moreno, David T Evans

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Although Nef is the viral gene product used by most simian immunodeficiency viruses to overcome restriction by tetherin, this activity was acquired by the Vpu protein of HIV-1 group M due to the absence of sequences in human tetherin that confer sus- ceptibility to Nef. Thus, it is widely accepted that HIV-1 group M uses Vpu instead of Nef to counteract tetherin. Challenging this paradigm, we identified Nef alleles of HIV-1 group M isolates with significant activity against human tetherin. These Nef pro- teins promoted virus release and tetherin downmodulation from the cell surface and, in the context of vpu-deleted HIV-1 recom- binants, enhanced virus replication and resistance to antibody-dependent cell-mediated cytotoxicity (ADCC). Further analysis revealed that the Vpu proteins from several of these viruses lack antitetherin activity, suggesting that under certain circum- stances, HIV-1 group M Nef may acquire the ability to counteract tetherin to compensate for the loss of this f
Original languageEnglish
JournalJournal of Virology
StatePublished - Sep 21 2016


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