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不只是性别问题:睾丸作为 HIV 的独特储存库及其对病毒清除的意义。

More than a Gender Issue: Testis as a Distinctive HIV Reservoir and Its Implication for Viral Eradication.

机构信息

Infectious Diseases and Immunity in Global Health Program, Research Institute, McGill University Health Centre, Montreal, QC, Canada.

Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada.

出版信息

Methods Mol Biol. 2022;2407:173-186. doi: 10.1007/978-1-0716-1871-4_13.

Abstract

Early establishment of HIV reservoir represents the main impediment to an HIV cure. Mainly composed of infected memory CD4 T-cells and macrophages, HIV reservoirs are found in several organs including lymph nodes, gut, and testes. In men, and as seen in brain and eyes, testes represent a distinctive organ characterized by an immune privilege, allowing the tolerance of spermatozoa which only develop after puberty, long after the establishment of systemic immunity. The immune privilege of testes relies on a strict testis-blood barrier, and a local immunosuppressive environment. Testes has been described as reservoir for several viruses including Ebola, Zika, and HIV. Indeed, HIV reservoirs were detected in tested viremic and virally suppressed donor taking antiretroviral therapy (ART). Herein, we discuss the distinctive environment found in human testes and describe a validated method allowing the characterization and quantification of HIV-infected CD4 T-cells in human testes. Using mechanical and enzymatic treatment, cells can be extracted from human testis samples. Characterization of those cells can be performed by flow cytometry and HIV reservoir quantification performed by nested qPCR after flow cytometry sorting.

摘要

早期建立的 HIV 储存库是 HIV 治愈的主要障碍。HIV 储存库主要由感染的记忆 CD4 T 细胞和巨噬细胞组成,存在于多个器官中,包括淋巴结、肠道和睾丸。在男性中,正如在大脑和眼睛中看到的那样,睾丸是一个独特的器官,具有免疫特权,允许对精子的耐受,而精子只有在青春期后才会发育,这远远晚于全身免疫的建立。睾丸的免疫特权依赖于严格的睾丸-血液屏障和局部免疫抑制环境。睾丸已被描述为包括埃博拉病毒、寨卡病毒和 HIV 在内的几种病毒的储存库。事实上,在接受抗逆转录病毒治疗 (ART) 的检测到病毒血症和病毒抑制的供体中检测到了 HIV 储存库。在此,我们讨论了在人类睾丸中发现的独特环境,并描述了一种经过验证的方法,允许对人类睾丸中的 HIV 感染的 CD4 T 细胞进行特征描述和定量。通过机械和酶处理,可以从人类睾丸样本中提取细胞。可以通过流式细胞术对这些细胞进行特征描述,并在流式细胞术分选后通过巢式 qPCR 进行 HIV 储存库定量。

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