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

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.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-0028-616B-9 Version Permalink: https://hdl.handle.net/11858/00-001M-0000-0028-616C-7
Genre: Journal Article

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 Creators:
Götz, N., Author
Sauter, D., Author
Usmani, S. M., Author
Fritz, J. V., Author
Goffinet, C., Author
Heigele, A., Author
Geyer, M.1, Author           
Bibollet-Ruche, F., Author
Learn, G. H., Author
Fackler, O. T., Author
Hahn, B. H., Author
Kirchhoff, F., Author
Affiliations:
1Research Group Physical Biochemistry, Center of Advanced European Studies and Research (caesar), Max Planck Society, ou_2173686              

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 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.

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Language(s): eng - English
 Dates: 2012
 Publication Status: Issued
 Pages: -
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 Rev. Type: -
 Identifiers: Other: 22980333
DOI: 10.1016/j.chom.2012.07.008
ISSN: 1934-6069 (Electronic)
ISSN: 1931-3128 (Linking)
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Title: Cell host & microbe
  Alternative Title : Cell Hoste Microbe
Source Genre: Journal
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Pages: - Volume / Issue: 12 (3) Sequence Number: - Start / End Page: 373 - 380 Identifier: -