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在抗逆转录病毒治疗期间，HIV-1 在淋巴结中通过细胞增殖得以维持。

HIV-1 in lymph nodes is maintained by cellular proliferation during antiretroviral therapy.

机构信息

HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, USA.

Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

出版信息

J Clin Invest. 2019 Jul 30;129(11):4629-4642. doi: 10.1172/JCI126714.

DOI:10.1172/JCI126714
PMID:31361603
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6819093/
Abstract

To investigate the possibility that HIV-1 replication in lymph nodes sustains the reservoir during ART, we looked for evidence of viral replication in 5 donors after up to 13 years of viral suppression. We characterized proviral populations in lymph nodes and peripheral blood before and during ART, evaluated the levels of viral RNA expression in single lymph node and blood cells, and characterized the proviral integration sites in paired lymph node and blood samples. Proviruses with identical sequences, identical integration sites, and similar levels of RNA expression were found in lymph nodes and blood samples collected during ART, and no single sequence with significant divergence from the pretherapy population was present in either blood or lymph nodes. These findings show that all detectable persistent HIV-1 infection is consistent with maintenance in lymph nodes by clonal proliferation of cells infected before ART and not by ongoing viral replication during ART.

摘要

为了探究 HIV-1 在淋巴结中的复制是否在抗逆转录病毒治疗（ART）期间维持了病毒库，我们在 5 名接受治疗长达 13 年的患者中寻找病毒复制的证据。我们在 ART 之前和期间对淋巴结和外周血中的前病毒群体进行了特征描述，评估了单个淋巴结和血细胞中的病毒 RNA 表达水平，并对配对的淋巴结和血液样本中的前病毒整合位点进行了特征描述。在 ART 期间采集的淋巴结和血液样本中发现了具有相同序列、相同整合位点和相似 RNA 表达水平的前病毒，并且在血液或淋巴结中都没有发现与治疗前群体有显著差异的单一序列。这些发现表明，所有可检测到的持续性 HIV-1 感染都是通过 ART 前感染的细胞的克隆增殖而在淋巴结中维持的，而不是通过 ART 期间的持续病毒复制。

相似文献

[1]
HIV-1 in lymph nodes is maintained by cellular proliferation during antiretroviral therapy.

J Clin Invest. 2019-7-30

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[3]
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[4]
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本文引用的文献

[1]
Clones of infected cells arise early in HIV-infected individuals.

JCI Insight. 2019-6-20

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No evidence of HIV replication in children on antiretroviral therapy.

J Clin Invest. 2017-10-2

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Virology. 2017-10

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SMS: Smart Model Selection in PhyML.

Mol Biol Evol. 2017-9-1

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Single-cell analysis of HIV-1 transcriptional activity reveals expression of proviruses in expanded clones during ART.

Proc Natl Acad Sci U S A. 2017-5-2

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