HIV efficiently infects T cells from the endometrium and remodels them to promote systemic viral spread
HIV efficiently infects T cells from the endometrium and remodels them to promote systemic viral spread
复制标题
DOI：
10.7554/elife.55487
复制
发表时间：
2020-05-26
期刊：
影响因子：
7.7
通讯作者：
Roan, Nadia R.
中科院分区：
文献类型：
--
作者：
Ma, Tongcui;Luo, Xiaoyu;Roan, Nadia R.
在艾滋病毒向妇女传播的过程中，女性生殖道(FRT)是最常见的感染部位，但病毒重塑使感染目标细胞的特征复杂化。在这里，我们报告了广泛的表型分析的艾滋病毒感染的子宫内膜细胞的细胞，并使用“最近邻”生物信息学的方法来追踪细胞，以其原始的感染前的表型。与血液中一样，HIV优先针对子宫内膜中的记忆CD4+T细胞，但这些细胞表现出独特的表型，并承受着更高的感染水平。HIV对生殖细胞的重塑包括下调TCR复合体成分和调节趋化因子受体的表达，以促进感染细胞向淋巴滤泡扩散。HIV还上调抗凋亡蛋白BIRC5，当BIRC5被阻断时，会促进受感染的子宫内膜细胞的死亡。这些结果表明，HIV重塑生殖器T细胞以延长生存能力并促进病毒传播，干扰这些过程可能会降低系统性病毒传播的可能性。
The female reproductive tract (FRT) is the most common site of infection during HIV transmission to women, but viral remodeling complicates characterization of cells targeted for infection. Here, we report extensive phenotypic analyses of HIV-infected endometrial cells by CyTOF, and use a 'nearest neighbor' bioinformatics approach to trace cells to their original pre-infection phenotypes. Like in blood, HIV preferentially targets memory CD4+ T cells in the endometrium, but these cells exhibit unique phenotypes and sustain much higher levels of infection. Genital cell remodeling by HIV includes downregulating TCR complex components and modulating chemokine receptor expression to promote dissemination of infected cells to lymphoid follicles. HIV also upregulates the anti-apoptotic protein BIRC5, which when blocked promotes death of infected endometrial cells. These results suggest that HIV remodels genital T cells to prolong viability and promote viral dissemination and that interfering with these processes might reduce the likelihood of systemic viral spread.