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Immune Activation Influences SAMHD1 Expression and Vpx-mediated SAMHD1 Degradation during Chronic HIV-1 Infection.
- Source :
-
Scientific reports [Sci Rep] 2016 Dec 06; Vol. 6, pp. 38162. Date of Electronic Publication: 2016 Dec 06. - Publication Year :
- 2016
-
Abstract
- SAMHD1 restricts human immunodeficiency virus type 1 (HIV-1) replication in myeloid cells and CD4 <superscript>+</superscript> T cells, while Vpx can mediate SAMHD1 degradation to promote HIV-1 replication. Although the restriction mechanisms of SAMHD1 have been well-described, SAMHD1 expression and Vpx-mediated SAMHD1 degradation during chronic HIV-1 infection were poorly understood. Flow cytometric analysis was used to directly visualize ex vivo, and after in vitro SIV-Vpx treatment, SAMHD1 expression in CD4 <superscript>+</superscript> T cells and monocytes. Here we report activated CD4 <superscript>+</superscript> T cells without SAMHD1 expression were severely reduced, and SAMHD1 in CD4 <superscript>+</superscript> T cells became susceptible to SIV-Vpx mediated degradation during chronic HIV-1 infection, which was absent from uninfected donors. These alterations were irreversible, even after long-term fully suppressive antiretroviral treatment. Although SAMHD1 expression in CD4 <superscript>+</superscript> T cells and monocytes was not found to correlate with plasma viral load, Vpx-mediated SAMHD1 degradation was associated with indicators of immune activation. In vitro assays further revealed that T-cell activation and an upregulated IFN-I pathway contributed to these altered SAMHD1 properties. These findings provide insight into how immune activation during HIV-1 infection leads to irreparable aberrations in restriction factors and in subsequent viral evasion from host antiviral defenses.
- Subjects :
- Adult
Aged
Anti-HIV Agents therapeutic use
Cell Line
Chronic Disease
Female
HIV Infections drug therapy
HIV Infections metabolism
HIV-1 pathogenicity
HIV-1 physiology
Host-Pathogen Interactions
Humans
Interferon-gamma metabolism
Male
Middle Aged
Proteolysis
SAM Domain and HD Domain-Containing Protein 1 genetics
SAM Domain and HD Domain-Containing Protein 1 immunology
Viral Load
Viral Regulatory and Accessory Proteins pharmacology
Virus Replication
HIV Infections immunology
SAM Domain and HD Domain-Containing Protein 1 metabolism
Viral Regulatory and Accessory Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 27922067
- Full Text :
- https://doi.org/10.1038/srep38162