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

doi:10.1016/j.chom.2012.07.008

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 journal › Article › Research › peer-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 language	English
Pages (from-to)	373-380
Number of pages	8
Journal	Cell Host and Microbe
Volume	12
Issue number	3
DOIs	https://doi.org/10.1016/j.chom.2012.07.008
Publication status	Published - 13 Sept 2012
Externally published	Yes

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Götz, N., Sauter, D., Usmani, S. M., Fritz, J. V., Goffinet, C., Heigele, A., Geyer, M., Bibollet-Ruche, F., Learn, G. H., Fackler, O. T., Hahn, B. H., & Kirchhoff, F. (2012). Reacquisition of nef-mediated tetherin antagonism in a single in vivo passage of HIV-1 through its original chimpanzee host. Cell Host and Microbe, 12(3), 373-380. https://doi.org/10.1016/j.chom.2012.07.008

@article{21b2714f4ba74c949df1ef805c048fae,

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

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.",

author = "Nicola G{\"o}tz and Daniel Sauter and Usmani, {Shariq M.} and Fritz, {Jo{\"e}lle V.} and Christine Goffinet and Anke Heigele and Matthias Geyer and Frederic Bibollet-Ruche and Learn, {Gerald H.} and Fackler, {Oliver T.} and Hahn, {Beatrice H.} and Frank Kirchhoff",

note = "Funding Information: We thank Susanne Engelhart, Kerstin Regensburger, and Martha Mayer for excellent technical assistance, Sebastian L{\"u}lf for help with structure depiction, and Jan M{\"u}nch for critical reading of the manuscript. TZM-bl cells were obtained through the NIH AIDS Research and Reference Reagent Program. This work was supported in part by the National Institutes of Health (R21 AI080364, R01 AI50529, R01 AI58715) and by the Deutsche Forschungsgemeinschaft (DFG; FA 378/11-1 to OTF and Leibniz award to F.K.). ",

year = "2012",

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Götz, N, Sauter, D, Usmani, SM, Fritz, JV, Goffinet, C, Heigele, A, Geyer, M, Bibollet-Ruche, F, Learn, GH, Fackler, OT, Hahn, BH & Kirchhoff, F 2012, 'Reacquisition of nef-mediated tetherin antagonism in a single in vivo passage of HIV-1 through its original chimpanzee host', Cell Host and Microbe, vol. 12, no. 3, pp. 373-380. https://doi.org/10.1016/j.chom.2012.07.008

TY - JOUR

T1 - Reacquisition of nef-mediated tetherin antagonism in a single in vivo passage of HIV-1 through its original chimpanzee host

AU - Götz, Nicola

AU - Sauter, Daniel

AU - Usmani, Shariq M.

AU - Fritz, Joëlle V.

AU - Goffinet, Christine

AU - Heigele, Anke

AU - Geyer, Matthias

AU - Bibollet-Ruche, Frederic

AU - Learn, Gerald H.

AU - Fackler, Oliver T.

AU - Hahn, Beatrice H.

AU - Kirchhoff, Frank

N1 - Funding Information: We thank Susanne Engelhart, Kerstin Regensburger, and Martha Mayer for excellent technical assistance, Sebastian Lülf for help with structure depiction, and Jan Münch for critical reading of the manuscript. TZM-bl cells were obtained through the NIH AIDS Research and Reference Reagent Program. This work was supported in part by the National Institutes of Health (R21 AI080364, R01 AI50529, R01 AI58715) and by the Deutsche Forschungsgemeinschaft (DFG; FA 378/11-1 to OTF and Leibniz award to F.K.).

PY - 2012/9/13

Y1 - 2012/9/13

N2 - 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.

AB - 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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U2 - 10.1016/j.chom.2012.07.008

DO - 10.1016/j.chom.2012.07.008

M3 - Article

C2 - 22980333

AN - SCOPUS:84866412071

SN - 1931-3128

VL - 12

SP - 373

EP - 380

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 3

ER -

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

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