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

Research output: Contribution to journalArticle


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


Cite this

Arias, J., Colomer-Lluch, M., Bredow, B. V., Greene, J., MacDonald, J., O'Connor, D., Serra Moreno, R., & Evans, D. T. (2016). Tetherin Antagonism by HIV-1 Group M Nef Proteins. Journal of Virology.