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Immune Activation Influences SAMHD1 Expression and Vpx-mediated SAMHD1 Degradation during Chronic HIV-1 Infection.


ABSTRACT: SAMHD1 restricts human immunodeficiency virus type 1 (HIV-1) replication in myeloid cells and CD4+ 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+ T cells and monocytes. Here we report activated CD4+ T cells without SAMHD1 expression were severely reduced, and SAMHD1 in CD4+ 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+ 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.

SUBMITTER: Fu W 

PROVIDER: S-EPMC5138643 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Immune Activation Influences SAMHD1 Expression and Vpx-mediated SAMHD1 Degradation during Chronic HIV-1 Infection.

Fu Weihui W   Qiu Chao C   Zhou Mingzhe M   Zhu Lingyan L   Yang Yu Y   Qiu Chenli C   Zhang Linxia L   Xu Xuan X   Wang Ying Y   Xu Jianqing J   Zhang Xiaoyan X  

Scientific reports 20161206


SAMHD1 restricts human immunodeficiency virus type 1 (HIV-1) replication in myeloid cells and CD4<sup>+</sup> 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<s  ...[more]

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