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

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 degra...

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Autores principales: Fu, Weihui, Qiu, Chao, Zhou, Mingzhe, Zhu, Lingyan, Yang, Yu, Qiu, Chenli, Zhang, Linxia, Xu, Xuan, Wang, Ying, Xu, Jianqing, Zhang, Xiaoyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5138643/
https://www.ncbi.nlm.nih.gov/pubmed/27922067
http://dx.doi.org/10.1038/srep38162
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author Fu, Weihui
Qiu, Chao
Zhou, Mingzhe
Zhu, Lingyan
Yang, Yu
Qiu, Chenli
Zhang, Linxia
Xu, Xuan
Wang, Ying
Xu, Jianqing
Zhang, Xiaoyan
author_facet Fu, Weihui
Qiu, Chao
Zhou, Mingzhe
Zhu, Lingyan
Yang, Yu
Qiu, Chenli
Zhang, Linxia
Xu, Xuan
Wang, Ying
Xu, Jianqing
Zhang, Xiaoyan
author_sort Fu, Weihui
collection PubMed
description 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.
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spelling pubmed-51386432016-12-16 Immune Activation Influences SAMHD1 Expression and Vpx-mediated SAMHD1 Degradation during Chronic HIV-1 Infection Fu, Weihui Qiu, Chao Zhou, Mingzhe Zhu, Lingyan Yang, Yu Qiu, Chenli Zhang, Linxia Xu, Xuan Wang, Ying Xu, Jianqing Zhang, Xiaoyan Sci Rep Article 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. Nature Publishing Group 2016-12-06 /pmc/articles/PMC5138643/ /pubmed/27922067 http://dx.doi.org/10.1038/srep38162 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Fu, Weihui
Qiu, Chao
Zhou, Mingzhe
Zhu, Lingyan
Yang, Yu
Qiu, Chenli
Zhang, Linxia
Xu, Xuan
Wang, Ying
Xu, Jianqing
Zhang, Xiaoyan
Immune Activation Influences SAMHD1 Expression and Vpx-mediated SAMHD1 Degradation during Chronic HIV-1 Infection
title Immune Activation Influences SAMHD1 Expression and Vpx-mediated SAMHD1 Degradation during Chronic HIV-1 Infection
title_full Immune Activation Influences SAMHD1 Expression and Vpx-mediated SAMHD1 Degradation during Chronic HIV-1 Infection
title_fullStr Immune Activation Influences SAMHD1 Expression and Vpx-mediated SAMHD1 Degradation during Chronic HIV-1 Infection
title_full_unstemmed Immune Activation Influences SAMHD1 Expression and Vpx-mediated SAMHD1 Degradation during Chronic HIV-1 Infection
title_short Immune Activation Influences SAMHD1 Expression and Vpx-mediated SAMHD1 Degradation during Chronic HIV-1 Infection
title_sort immune activation influences samhd1 expression and vpx-mediated samhd1 degradation during chronic hiv-1 infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5138643/
https://www.ncbi.nlm.nih.gov/pubmed/27922067
http://dx.doi.org/10.1038/srep38162
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