Stieh Daniel J, Matias Edgar, Xu Huanbin, Fought Angela J, Blanchard James L, Marx Preston A, Veazey Ronald S, Hope Thomas J
Department of Cellular and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433, USA.
Cell Host Microbe. 2016 Apr 13;19(4):529-40. doi: 10.1016/j.chom.2016.03.005.
The difficulty in detecting rare infected cells immediately after mucosal HIV transmission has hindered our understanding of the initial cells targeted by the virus. Working with the macaque simian immunodeficiency virus (SIV) vaginal challenge model, we developed methodology to identify discrete foci of SIV (mac239) infection 48 hr after vaginal inoculation. We find infectious foci throughout the reproductive tract, from labia to ovary. Phenotyping infected cells reveals that SIV has a significant bias for infection of CCR6+ CD4+ T cells. SIV-infected cells expressed the transcriptional regulator RORγt, confirming that the initial target cells are specifically of the Th17 lineage. Furthermore, we detect host responses to infection, as evidenced by apoptosis, cell lysis, and phagocytosis of infected cells. Thus, our analysis identifies Th17-lineage CCR6+ CD4+ T cells as primary targets of SIV during vaginal transmission. This opens new opportunities for interventions to protect these cells and prevent HIV transmission.
在黏膜HIV传播后立即检测罕见感染细胞存在困难，这阻碍了我们对病毒最初靶向细胞的理解。利用猕猴猿猴免疫缺陷病毒（SIV）阴道攻击模型，我们开发了一种方法，用于在阴道接种后48小时识别SIV（mac239）感染的离散病灶。我们在整个生殖道中发现了感染病灶，从阴唇到卵巢。对感染细胞进行表型分析表明，SIV对CCR6 + CD4 + T细胞感染存在显著偏好。SIV感染的细胞表达转录调节因子RORγt，证实最初的靶细胞具体为Th17谱系。此外，我们检测到宿主对感染的反应，表现为感染细胞的凋亡、细胞裂解和吞噬作用。因此，我们的分析确定Th17谱系CCR6 + CD4 + T细胞是阴道传播过程中SIV的主要靶细胞。这为保护这些细胞并预防HIV传播的干预措施开辟了新机会。
