脂肪组织储存库中的 HIV 持续存在。
HIV Persistence in Adipose Tissue Reservoirs.
机构信息
Division of Infectious Diseases, Department of Internal Medicine, The University of Texas Health Science Center at Houston, 6431 Fannin St., MSB 2.112, Houston, TX, 77030, USA.
出版信息
Curr HIV/AIDS Rep. 2018 Feb;15(1):60-71. doi: 10.1007/s11904-018-0378-z.
PURPOSE OF REVIEW
The purpose of this review is to examine the evidence describing adipose tissue as a reservoir for HIV-1 and how this often expansive anatomic compartment contributes to HIV persistence.
RECENT FINDINGS
Memory CD4 T cells and macrophages, the major host cells for HIV, accumulate in adipose tissue during HIV/SIV infection of humans and rhesus macaques. Whereas HIV and SIV proviral DNA is detectable in CD4 T cells of multiple fat depots in virtually all infected humans and monkeys examined, viral RNA is less frequently detected, and infected macrophages may be less prevalent in adipose tissue. However, based on viral outgrowth assays, adipose-resident CD4 T cells are latently infected with virus that is replication-competent and infectious. Additionally, adipocytes interact with CD4 T cells and macrophages to promote immune cell activation and inflammation which may be supportive for HIV persistence. Antiviral effector cells, such as CD8 T cells and NK/NKT cells, are abundant in adipose tissue during HIV/SIV infection and typically exceed CD4 T cells, whereas B cells are largely absent from adipose tissue of humans and monkeys. Additionally, CD8 T cells in adipose tissue of HIV patients are activated and have a late differentiated phenotype, with unique TCR clonotypes of less diversity relative to blood CD8 T cells. With respect to the distribution of antiretroviral drugs in adipose tissue, data is limited, but there may be class-specific penetration of fat depots. The trafficking of infected immune cells within adipose tissues is a common event during HIV/SIV infection of humans and monkeys, but the virus may be mostly transcriptionally dormant. Viral replication may occur less in adipose tissue compared to other major reservoirs, such as lymphoid tissue, but replication competence and infectiousness of adipose latent virus are comparable to other tissues. Due to the ubiquitous nature of adipose tissue, inflammatory interactions among adipocytes and CD4 T cells and macrophages, and selective distribution of antiretroviral drugs, the sequestration of infected immune cells within fat depots likely represents a major challenge for cure efforts.
目的综述
本综述旨在探讨脂肪组织作为 HIV-1 储存库的证据，以及这个广泛的解剖部位如何促进 HIV 持续存在。
最近的发现
在人类和恒河猴感染 HIV/SIV 期间，记忆性 CD4 T 细胞和巨噬细胞（HIV 的主要宿主细胞）在脂肪组织中积累。虽然在几乎所有接受检查的受感染人类和猴子的多个脂肪库的 CD4 T 细胞中都能检测到 HIV 和 SIV 前病毒 DNA，但病毒 RNA 较少被检测到，并且感染的巨噬细胞在脂肪组织中可能不太常见。然而，基于病毒扩增试验，脂肪组织中驻留的 CD4 T 细胞被潜伏感染了具有复制能力和传染性的病毒。此外，脂肪细胞与 CD4 T 细胞和巨噬细胞相互作用，促进免疫细胞激活和炎症，这可能有助于 HIV 持续存在。在 HIV/SIV 感染期间，抗病毒效应细胞（如 CD8 T 细胞和 NK/NKT 细胞）在脂肪组织中丰富，通常超过 CD4 T 细胞，而 B 细胞在人类和猴子的脂肪组织中基本不存在。此外，HIV 患者脂肪组织中的 CD8 T 细胞被激活，具有晚期分化表型，与血液 CD8 T 细胞相比，TCR 克隆型的多样性较低。关于抗逆转录病毒药物在脂肪组织中的分布，数据有限，但可能存在脂肪沉积的特定药物渗透。在人类和猴子感染 HIV/SIV 期间，感染免疫细胞在脂肪组织中的运输是一种常见现象，但病毒可能主要处于转录休眠状态。与其他主要储存库（如淋巴组织）相比，脂肪组织中的病毒复制可能较少，但脂肪潜伏病毒的复制能力和传染性与其他组织相当。由于脂肪组织无处不在，脂肪细胞与 CD4 T 细胞和巨噬细胞之间的炎症相互作用，以及抗逆转录病毒药物的选择性分布，感染免疫细胞在脂肪组织中的隔离很可能是治愈努力的主要挑战。
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