Yu, Hangxing;
Usmani, Shariq M;
Borch, Alexandra;
Krämer, Julia;
Stürzel, Christina M;
Khalid, Mohammad;
Li, Xuehua;
Krnavek, Daniela;
van der Ende, Marchina E;
Osterhaus, Albert D;
Gruters, Rob A;
Kirchhoff, Frank
The efficiency of Vpx-mediated SAMHD1 antagonism does not correlate with the potency of viral control in HIV-2-infected individuals
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Medientyp:
E-Artikel
Titel:
The efficiency of Vpx-mediated SAMHD1 antagonism does not correlate with the potency of viral control in HIV-2-infected individuals
Beteiligte:
Yu, Hangxing;
Usmani, Shariq M;
Borch, Alexandra;
Krämer, Julia;
Stürzel, Christina M;
Khalid, Mohammad;
Li, Xuehua;
Krnavek, Daniela;
van der Ende, Marchina E;
Osterhaus, Albert D;
Gruters, Rob A;
Kirchhoff, Frank
Erschienen:
Springer Science and Business Media LLC, 2013
Erschienen in:
Retrovirology, 10 (2013) 1
Sprache:
Englisch
DOI:
10.1186/1742-4690-10-27
ISSN:
1742-4690
Entstehung:
Anmerkungen:
Beschreibung:
AbstractBackgroundThe presence of avpxgene distinguishes HIV-2 from HIV-1, the main causative agent of AIDS. Vpx degrades the restriction factor SAMHD1 to boost HIV-2 infection of macrophages and dendritic cells and it has been suggested that the activation of antiviral innate immune responses after Vpx-dependent infection of myeloid cells may explain why most HIV-2-infected individuals efficiently control viral replication and become long-term survivors. However, the role of Vpx-mediated SAMHD1 antagonism in the virological and clinical outcome of HIV-2 infection remained to be investigated.ResultsHere, we analyzed the anti-SAMHD1 activity ofvpxalleles derived from seven viremic and four long-term aviremic HIV-2-infected individuals. We found that effective Vpx-mediated SAMHD1 degradation and enhancement of myeloid cell infection was preserved in most HIV-2-infected individuals including all seven that failed to control the virus and developed AIDS. The only exception werevpxalleles from an aviremic individual that predicted a M68K change in a highly conserved nuclear localization signal which disrupted the ability of Vpx to counteract SAMHD1. We also found that HIV-2 is less effective than HIV-1 in inducing innate immune activation in dendritic cells.ConclusionsEffective immune control of viral replication in HIV-2-infected individuals is not associated with increased Vpx-mediated degradation of SAMHD1.