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- Title
The efficiency of Vpx-mediated SAMHD1 antagonism does not correlate with the potency of viral control in HIV-2-infected individuals.
- Authors
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
- Abstract
Background: The presence of a vpx gene 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. Results: Here, we analyzed the anti-SAMHD1 activity of vpx alleles 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 were vpx alleles 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. Conclusions: Effective immune control of viral replication in HIV-2-infected individuals is not associated with increased Vpx-mediated degradation of SAMHD1.
- Subjects
THERAPEUTICS; HIV infections; ANTIVIRAL agents; NATURAL immunity; VIRAL replication; MACROPHAGES; TREATMENT effectiveness; AIDS treatment; DRUG antagonism
- Publication
Retrovirology, 2013, Vol 10, Issue 1, p1
- ISSN
1742-4690
- Publication type
Article
- DOI
10.1186/1742-4690-10-27