Reacquisition of nef-mediated tetherin antagonism in a single in vivo passage of HIV-1 through its original chimpanzee host

Nicola Götz, Daniel Sauter, Shariq M. Usmani, Joëlle V. Fritz, Christine Goffinet, Anke Heigele, Matthias Geyer, Frederic Bibollet-Ruche, Gerald H. Learn, Oliver T. Fackler, Beatrice H. Hahn, Frank Kirchhoff*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

30 Citations (Scopus)

Abstract

The interferon-induced host restriction factor tetherin poses a barrier for SIV transmission from primates to humans. After cross-species transmission, the chimpanzee precursor of pandemic HIV-1 switched from the accessory protein Nef to Vpu to effectively counteract human tetherin. As we report here, the experimental reintroduction of HIV-1 into its original chimpanzee host resulted in a virus that can use both Vpu and Nef to antagonize chimpanzee tetherin. Functional analyses demonstrated that alterations in and near the highly conserved ExxxLL motif in the C-terminal loop of Nef were critical for the reacquisition of antitetherin activity. Strikingly, just two amino acid changes allowed HIV-1 Nef to counteract chimpanzee tetherin and promote virus release. Our data demonstrate that primate lentiviruses can reacquire lost accessory gene functions during a single in vivo passage and suggest that other functional constraints keep Nef ready to regain antitetherin activity.

Original languageEnglish
Pages (from-to)373-380
Number of pages8
JournalCell Host and Microbe
Volume12
Issue number3
DOIs
Publication statusPublished - 13 Sep 2012
Externally publishedYes

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