Nef proteins of epidemic HIV-1 group O strains antagonize human tetherin

Silvia F. Kluge; Katharina Mack; Shilpa S. Iyer; François M. Pujol; Anke Heigele; Gerald H. Learn; Shariq M. Usmani; Daniel Sauter; Simone Joas; Dominik Hotter; Frederic Bibollet-Ruche; Lindsey J. Plenderleith; Martine Peeters; Matthias Geyer; Paul M. Sharp; Oliver T. Fackler; Beatrice H. Hahn; Frank Kirchhoff

doi:10.1016/j.chom.2014.10.002

Nef proteins of epidemic HIV-1 group O strains antagonize human tetherin

Silvia F. Kluge, Katharina Mack, Shilpa S. Iyer, François M. Pujol, Anke Heigele, Gerald H. Learn, Shariq M. Usmani, Daniel Sauter, Simone Joas, Dominik Hotter, Frederic Bibollet-Ruche, Lindsey J. Plenderleith, Martine Peeters, Matthias Geyer, Paul M. Sharp, Oliver T. Fackler, Beatrice H. Hahn^*, Frank Kirchhoff

^*Corresponding author for this work

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

Most simian immunodeficiency viruses use their Nef protein to antagonize the host restriction factor tetherin. A deletion in human tetherin confers Nef resistance, representing a hurdle to successful zoonotic transmission. HIV-1 group M evolved to utilize the viral protein U (Vpu) to counteract tetherin. Although HIV-1 group O has spread epidemically in humans, it has not evolved a Vpu-based tetherin antagonism. Here we show that HIV-1 group O Nef targets a region adjacent to this deletion to inhibit transport of human tetherin to the cell surface, enhances virion release, and increases viral resistance to inhibition by interferon-α. The Nef protein of the inferred common ancestor of group O viruses is also active against human tetherin. Thus, Nef-mediated antagonism of human tetherin evolved prior to the spread of HIV-1 group O and likely facilitated secondary virus transmission. Our results may explain the epidemic spread of HIV-1 group O.

Original language	English
Pages (from-to)	639-650
Number of pages	12
Journal	Cell Host & Microbe
Volume	16
Issue number	5
DOIs	https://doi.org/10.1016/j.chom.2014.10.002
Publication status	Published - 12 Nov 2014

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Kluge, S. F., Mack, K., Iyer, S. S., Pujol, F. M., Heigele, A., Learn, G. H., Usmani, S. M., Sauter, D., Joas, S., Hotter, D., Bibollet-Ruche, F., Plenderleith, L. J., Peeters, M., Geyer, M., Sharp, P. M., Fackler, O. T., Hahn, B. H., & Kirchhoff, F. (2014). Nef proteins of epidemic HIV-1 group O strains antagonize human tetherin. Cell Host & Microbe, 16(5), 639-650. https://doi.org/10.1016/j.chom.2014.10.002

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title = "Nef proteins of epidemic HIV-1 group O strains antagonize human tetherin",

abstract = "Most simian immunodeficiency viruses use their Nef protein to antagonize the host restriction factor tetherin. A deletion in human tetherin confers Nef resistance, representing a hurdle to successful zoonotic transmission. HIV-1 group M evolved to utilize the viral protein U (Vpu) to counteract tetherin. Although HIV-1 group O has spread epidemically in humans, it has not evolved a Vpu-based tetherin antagonism. Here we show that HIV-1 group O Nef targets a region adjacent to this deletion to inhibit transport of human tetherin to the cell surface, enhances virion release, and increases viral resistance to inhibition by interferon-α. The Nef protein of the inferred common ancestor of group O viruses is also active against human tetherin. Thus, Nef-mediated antagonism of human tetherin evolved prior to the spread of HIV-1 group O and likely facilitated secondary virus transmission. Our results may explain the epidemic spread of HIV-1 group O.",

author = "Kluge, {Silvia F.} and Katharina Mack and Iyer, {Shilpa S.} and Pujol, {Fran{\c c}ois M.} and Anke Heigele and Learn, {Gerald H.} and Usmani, {Shariq M.} and Daniel Sauter and Simone Joas and Dominik Hotter and Frederic Bibollet-Ruche and Plenderleith, {Lindsey J.} and Martine Peeters and Matthias Geyer and Sharp, {Paul M.} and Fackler, {Oliver T.} and Hahn, {Beatrice H.} and Frank Kirchhoff",

year = "2014",

month = nov,

day = "12",

doi = "10.1016/j.chom.2014.10.002",

language = "English",

volume = "16",

pages = "639--650",

journal = "Cell Host & Microbe",

issn = "1931-3128",

publisher = "Cell Press",

number = "5",

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Kluge, SF, Mack, K, Iyer, SS, Pujol, FM, Heigele, A, Learn, GH, Usmani, SM, Sauter, D, Joas, S, Hotter, D, Bibollet-Ruche, F, Plenderleith, LJ, Peeters, M, Geyer, M, Sharp, PM, Fackler, OT, Hahn, BH & Kirchhoff, F 2014, 'Nef proteins of epidemic HIV-1 group O strains antagonize human tetherin', Cell Host & Microbe, vol. 16, no. 5, pp. 639-650. https://doi.org/10.1016/j.chom.2014.10.002

TY - JOUR

T1 - Nef proteins of epidemic HIV-1 group O strains antagonize human tetherin

AU - Kluge, Silvia F.

AU - Mack, Katharina

AU - Iyer, Shilpa S.

AU - Pujol, François M.

AU - Heigele, Anke

AU - Learn, Gerald H.

AU - Usmani, Shariq M.

AU - Sauter, Daniel

AU - Joas, Simone

AU - Hotter, Dominik

AU - Bibollet-Ruche, Frederic

AU - Plenderleith, Lindsey J.

AU - Peeters, Martine

AU - Geyer, Matthias

AU - Sharp, Paul M.

AU - Fackler, Oliver T.

AU - Hahn, Beatrice H.

AU - Kirchhoff, Frank

PY - 2014/11/12

Y1 - 2014/11/12

N2 - Most simian immunodeficiency viruses use their Nef protein to antagonize the host restriction factor tetherin. A deletion in human tetherin confers Nef resistance, representing a hurdle to successful zoonotic transmission. HIV-1 group M evolved to utilize the viral protein U (Vpu) to counteract tetherin. Although HIV-1 group O has spread epidemically in humans, it has not evolved a Vpu-based tetherin antagonism. Here we show that HIV-1 group O Nef targets a region adjacent to this deletion to inhibit transport of human tetherin to the cell surface, enhances virion release, and increases viral resistance to inhibition by interferon-α. The Nef protein of the inferred common ancestor of group O viruses is also active against human tetherin. Thus, Nef-mediated antagonism of human tetherin evolved prior to the spread of HIV-1 group O and likely facilitated secondary virus transmission. Our results may explain the epidemic spread of HIV-1 group O.

AB - Most simian immunodeficiency viruses use their Nef protein to antagonize the host restriction factor tetherin. A deletion in human tetherin confers Nef resistance, representing a hurdle to successful zoonotic transmission. HIV-1 group M evolved to utilize the viral protein U (Vpu) to counteract tetherin. Although HIV-1 group O has spread epidemically in humans, it has not evolved a Vpu-based tetherin antagonism. Here we show that HIV-1 group O Nef targets a region adjacent to this deletion to inhibit transport of human tetherin to the cell surface, enhances virion release, and increases viral resistance to inhibition by interferon-α. The Nef protein of the inferred common ancestor of group O viruses is also active against human tetherin. Thus, Nef-mediated antagonism of human tetherin evolved prior to the spread of HIV-1 group O and likely facilitated secondary virus transmission. Our results may explain the epidemic spread of HIV-1 group O.

U2 - 10.1016/j.chom.2014.10.002

DO - 10.1016/j.chom.2014.10.002

M3 - Article

C2 - 25525794

AN - SCOPUS:84910631057

SN - 1931-3128

VL - 16

SP - 639

EP - 650

JO - Cell Host & Microbe

JF - Cell Host & Microbe

IS - 5

ER -

Nef proteins of epidemic HIV-1 group O strains antagonize human tetherin

Abstract

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