Establishment, Persistence, and Reactivation of Latent HIV-1 Infection in Renal Epithelial Cells
HIV-1 persistence in different cell types presents the main obstacle to an HIV-1 cure. We have previously shown that the renal epithelium is a site of HIV-1 infection and that the kidney represents a separate viral compartment from blood. Whether renal cells can harbor latent virus that can be reactivated upon treatment with latency reversing agents (LRAs) is unknown. To address this question, we developed an in vitro HIV-1 latency model in renal tubule epithelial (RTE) cells using a dual color HIV-1 reporter virus, R7/E-/GFP/EF1a-mCherry (R7GEmC), and evaluated the effect of LRAs, both as single agents and in combination, on viral reactivation. Our data show that HIV-1 can establish latency in RTE cells early postinfection. While the pool of latently infected cells expanded overtime, the percentage of productively infected cells declined. Following LRA treatment only a small fraction of latently infected cells, both T cells and RTE cells, could be reactivated, and the drug combinations more effective in reactivating HIV transcription in RTE cells differed from those more active in T cells. Our study demonstrates that HIV can establish latency in RTE cells and that current LRAs are only marginally effective in inducing HIV-1 reactivation. This suggests that further study of LRA dynamics in non-T cells may be warranted to assess the suitability of LRAs as a sterilizing cure strategy. IMPORTANCE Anti-retroviral therapy (ART) has dramatically reduced HIV-related morbidity and mortality. Despite this success, a number of challenges remain, including the long-term persistence of multiple, clinically latent viral reservoirs capable of reactivation in the absence of ART. As efforts proceed toward HIV eradication or functional cure, further understanding of the dynamics of HIV-1 replication, establishment of latency and mechanisms of reactivation in reservoirs harboring the virus throughout the body is necessary. HIV-1 can infect renal epithelial cells and the expression of viral genes in those cells contributes to the development of HIV associated nephropathy (HIVAN) in untreated individuals. The significance of our work is in developing the first model of HIV-1 latency in renal epithelial cells. This model enhances our understanding of HIV-1 latency and persistence in the kidney and can be used to screen candidate latency reversing agents.Keywords: HIV-1; LRAs; latency; renal epithelial cells; reservoir.
乐备实(上海优宁维生物科技股份有限公司旗下全资子公司),是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家,自2018年成立以来,乐备实不断寻求突破,公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个,建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。
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