Reacquisition of nef-mediated tetherin antagonism in a single in vivo passage of HIV-1 through its original chimpanzee host
Summary. 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 r...
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| Hauptverfasser: | , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
13 September 2012
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| In: |
Cell host and microbe
Year: 2012, Jahrgang: 12, Heft: 3, Pages: 373-380 |
| ISSN: | 1934-6069 |
| DOI: | 10.1016/j.chom.2012.07.008 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1016/j.chom.2012.07.008 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1931312812002417 
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| Verfasserangaben: | 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, and Frank Kirchhoff |
MARC
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| 245 | 1 | 0 | |a Reacquisition of nef-mediated tetherin antagonism in a single in vivo passage of HIV-1 through its original chimpanzee host |c 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, and Frank Kirchhoff |
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| 520 | |a Summary. 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. | ||
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