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The efficiency of Vpx-mediated SAMHD1 antagonism does not correlate with the potency of viral control in HIV-2-infected individuals
- Source :
- Retrovirology, Retrovirology, 10. BioMed Central Ltd.
- Publication Year :
- 2012
-
Abstract
- BackgroundThe 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.
- Subjects :
- Myeloid
Viral immune sensing
Cell
Molecular Sequence Data
HIV Infections
Virus Replication
Virus
Cell Line
SAM Domain and HD Domain-Containing Protein 1
Vpx
SDG 3 - Good Health and Well-being
Virology
medicine
Cluster Analysis
Humans
Viral Regulatory and Accessory Proteins
Amino Acid Sequence
Gene
Phylogeny
Monomeric GTP-Binding Proteins
Innate immune system
biology
Research
Dendritic Cells
Sequence Analysis, DNA
SAMHD1
AIDS
Infectious Diseases
medicine.anatomical_structure
Viral replication
Immunology
HIV-2
Host-Pathogen Interactions
Proteolysis
biology.protein
Antibody
Subjects
Details
- ISSN :
- 17424690
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Retrovirology
- Accession number :
- edsair.doi.dedup.....ef5ddc2d15939ae641cdd73184acd7c2