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

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Geyer,  M.
Research Group Physical Biochemistry, Center of Advanced European Studies and Research (caesar), Max Planck Society;

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Citation

Götz, N., Sauter, D., Usmani, S. M., Fritz, J. V., Goffinet, C., Heigele, A., et al. (2012). Reacquisition of Nef-mediated tetherin antagonism in a single in vivo passage of HIV-1 through its original chimpanzee host. Cell host & microbe, 12(3), 373-380. doi:10.1016/j.chom.2012.07.008.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0028-616B-9
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.