期刊
MICROBES AND INFECTION
卷 23, 期 1, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.micinf.2020.10.003
关键词
HIV; Humanized mice; CD4 T cells; Pyroptosis; Necroptosis; Apoptosis
资金
- JSPS KAKENHI [JP17K08800]
- ViiV healthcare Japan Research Grant
Various types of non-apoptotic CD4 T-cell death, such as pyroptosis and necroptosis, are induced during the early phase of HIV infection in vivo, indicating a complex mechanism of CD4 T-cell depletion.
Several mechanisms underline induction of CD4 T-cell death by human immunodeficiency virus (HIV) infection. For a long time, apoptosis was considered central to cell death involved in the depletion of CD4 T cells during HIV infection. However, which types of cell death are induced during the early phase of HIV infection in vivo remains unclear. In this study, CD4 T-cell death induced in early HIV infection was characterized using humanized mice challenged with CCR5-tropic (R5) or CXCR4-tropic (X4) HIV-1. Results showed that CD4 T-cell death was induced in the spleen 3 days post-challenge with both R5 and X4 HIV-1. Although cell death without caspase-1 and caspase-3/7 activation was preferentially observed, caspase-1(+) pyroptosis was also significantly induced within the memory subpopulation by R5 or X4 HIV-1 and the naive subpopulation by X4 HIV-1. In contrast, caspase-3/7(+) apoptosis was not enhanced by either R5 or X4 HIV-1. Furthermore, phosphorylated mixed lineage kinase domain-like protein(+) necroptosis was induced by only X4 HIV-1. These findings indicate that various types of non-apoptotic CD4 T-cell death, such as pyroptosis and necroptosis, are induced during the early phase of HIV infection in vivo. (C) 2020 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
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