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

Silvia F Kluge1, Katharina Mack1, Shilpa S Iyer2

  • 1Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.

Cell Host & Microbe
|December 20, 2014
PubMed

Insights

HIV-1 group O uses its Nef protein to overcome human tetherin restriction, unlike HIV-1 group M which uses Vpu. This Nef-mediated antagonism likely facilitated the epidemic spread of HIV-1 group O.

Area of Science:

  • Virology
  • Immunology
  • Evolutionary Biology

Background:

  • Simian immunodeficiency viruses (SIVs) antagonize host tetherin using Nef protein.
  • Human tetherin possesses a deletion conferring resistance to Nef, hindering zoonotic transmission.
  • HIV-1 group M evolved Vpu to counteract tetherin, while HIV-1 group O lacks Vpu-based antagonism.

Purpose of the Study:

  • To investigate the mechanism by which HIV-1 group O antagonizes human tetherin.
  • To determine if HIV-1 group O Nef targets human tetherin and if this evolved prior to epidemic spread.

Main Methods:

  • Analyzing the interaction between HIV-1 group O Nef and human tetherin.
  • Assessing the impact of Nef on tetherin cell surface transport and virion release.
  • Evaluating viral resistance to interferon-α inhibition.

Main Results:

  • HIV-1 group O Nef inhibits human tetherin transport to the cell surface by targeting a region adjacent to the resistance-conferring deletion.
  • Nef enhances virion release and increases viral resistance to interferon-α.
  • The Nef protein of the inferred common ancestor of group O viruses also antagonizes human tetherin.

Conclusions:

  • Nef-mediated antagonism of human tetherin predates the epidemic spread of HIV-1 group O.
  • This ancient Nef function likely facilitated secondary virus transmission and may explain the epidemic spread of HIV-1 group O.

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