文章基本信息

标题：Immune Activation Influences SAMHD1 Expression and Vpx-mediated SAMHD1 Degradation during Chronic HIV-1 Infection
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作者：Weihui Fu ; Chao Qiu ; Mingzhe Zhou 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2016
卷号：6
期号：1
DOI：10.1038/srep38162
语种：English
出版社：Springer Nature
摘要：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.