Tetherin antagonism by HIV-1 group M Nef proteins

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

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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 groupMdue to the absence of sequences in human tetherin that confer susceptibility to Nef. Thus, it is widely accepted that HIV-1 groupMuses Vpu instead of Nef to counteract tetherin. Challenging this paradigm, we identified Nef alleles of HIV-1 groupMisolates with significant activity against human tetherin. These Nef proteins promoted virus release and tetherin downmodulation from the cell surface and, in the context of vpu-deleted HIV-1 recombinants, 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 circumstances, HIV-1 groupMNef may acquire the ability to counteract tetherin to compensate for the loss of this function by Vpu. These observations illustrate the remarkable plasticity of HIV-1 in overcoming restriction by tetherin and challenge the prevailing view that all HIV-1 groupMisolates use Vpu to counteract tetherin.

Original languageEnglish
Pages (from-to)10701-10714
Number of pages14
JournalJournal of Virology
Issue number23
StatePublished - 2016


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