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

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Abstract

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
Volume90
Issue number23
DOIs
StatePublished - Jan 1 2016

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Arias, J. F., Colomer-Lluch, M., Bredow, B. V., Greene, J. M., MacDonald, J., O'Connor, D. H., Serra-Moreno, R., & Evans, D. T. (2016). Tetherin antagonism by HIV-1 group M Nef proteins. Journal of Virology, 90(23), 10701-10714. https://doi.org/10.1128/JVI.01465-16