Tetherin-Driven Adaptation of Vpu and Nef Function and the Evolution of Pandemic and Nonpandemic HIV-1 Strains

Daniel Sauter, Michael Schindler, Anke Specht, Wilmina N. Landford, Jan Muench, Kyeong-Ae Kim, Joerg Votteler, Ulrich Schubert, Frederic Bibollet-Ruche, Brandon F. Keele, Jun Takehisa, Yudelca Ogando, Christina Ochsenbauer, John C. Kappes, Ahidjo Ayouba, Martine Peeters, Gerald H. Learn, George Shaw, Paul M. Sharp, Paul BieniaszBeatrice H. Hahn, Theodora Hatziioannou, Frank Kirchhoff

Research output: Contribution to journalArticlepeer-review

Abstract

Vpu proteins of pandemic HIV-1 M strains degrade the viral receptor CD4 and antagonize human tetherin to promote viral release and replication. We show that Vpus from SIVgsn, SIVmus, and SIVmon infecting Cercopithecus primate species also degrade CD4 and antagonize tetherin. In contrast, SIVcpz, the immediate precursor of HIV-1, whose Vpu shares a common ancestry with SIVgsn/mus/mon Vpu, uses Nef rather than Vpu to counteract chimpanzee tetherin. Human tetherin, however, is resistant to Nef and thus poses a significant barrier to zoonotic transmission of SIVcpz to humans. Remarkably, Vpus from nonpandemic HIV-1 0 strains are poor tetherin antagonists, whereas those from the rare group N viruses do not degrade CD4. Thus, only HIV-1 M evolved a fully functional Vpu following the three independent cross-species transmissions that resulted in HIV-1 groups M, N, and O. This may explain why group M viruses are almost entirely responsible for the global HIV/AIDS pandemic.

Original languageEnglish
Pages (from-to)409-421
Number of pages13
JournalCell Host & Microbe
Volume6
Issue number5
DOIs
Publication statusPublished - 19 Nov 2009

Cite this