Neurosymptomatic HIV-1 CSF escape is associated with replication in CNS T cells and inflammation.

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Laura P Kincer, Ameet Dravid, Mattia Trunfio, Andrea Calcagno, Shuntai Zhou, Riccardo Vercesi, Serena Spudich, Magnus Gisslen, Richard W Price, Paola Cinque, Sarah B Joseph
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引用次数: 0

Abstract

During antiretroviral therapy (ART), most people living with HIV-1 have undetectable HIV-1 RNA in their plasma. However, they occasionally present with new or progressive neurologic deficits and detectable HIV-1 RNA in the cerebrospinal fluid (CSF), a condition defined as neurosymptomatic HIV-1 CSF escape (NSE). We explored the source of neuropathogenesis and HIV-1 RNA in the CSF during NSE by characterizing HIV-1 populations and inflammatory biomarkers in CSF from 25 individuals with NSE. HIV-1 populations in the CSF were uniformly drug resistant and adapted to replication in CD4+ T cells, but differed greatly in genetic diversity, with some having low levels of diversity similar to those observed during untreated primary infection and others having high levels like those during untreated chronic infection. Higher diversity in the CSF during NSE was associated with greater CNS inflammation. Finally, optimization of ART regimen was associated with viral suppression and improvement of neurologic symptoms. These results are consistent with CNS inflammation and neurologic injury during NSE being driven by replication of partially drug-resistant virus in CNS CD4+ T cells. This is unlike nonsuppressible viremia in the plasma during ART, which typically lacks clinical consequences and is generated by virus expression without replication.

有神经症状的 HIV-1 CSF 逸出与中枢神经系统 T 细胞的复制和炎症有关。
在抗逆转录病毒疗法(ART)期间,大多数 HIV-1 感染者的血浆中检测不到 HIV-1 RNA。然而,他们偶尔会出现新的或进行性神经功能缺损,并在脑脊液(CSF)中检测到 HIV-1 RNA,这种情况被定义为神经症状性 HIV-1 CSF 逸出症(NSE)。我们通过分析 25 名 NSE 患者脑脊液中的 HIV-1 群体和炎症生物标志物,探索了 NSE 期间神经发病机制和脑脊液中 HIV-1 RNA 的来源。CSF中的HIV-1种群具有一致的耐药性,并适应在CD4+ T细胞中复制,但在遗传多样性方面却有很大差异,其中一些种群的多样性水平较低,与未经治疗的原发性感染期间所观察到的相似,而另一些则与未经治疗的慢性感染期间所观察到的相似,具有较高的多样性水平。NSE 期间 CSF 中较高的多样性与较严重的中枢神经系统炎症有关。最后,抗逆转录病毒疗法的优化与病毒抑制和神经系统症状的改善有关。这些结果与 NSE 期间中枢神经系统炎症和神经系统损伤是由中枢神经系统 CD4+ T 细胞中部分耐药病毒的复制驱动一致。这与抗逆转录病毒疗法期间血浆中的非抑制性病毒血症不同,后者通常没有临床后果,是由病毒表达而非复制产生的。
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来源期刊
Journal of Clinical Investigation
Journal of Clinical Investigation 医学-医学:研究与实验
CiteScore
24.50
自引率
1.30%
发文量
1034
审稿时长
2 months
期刊介绍: The Journal of Clinical Investigation, established in 1924 by the ASCI, is a prestigious publication that focuses on breakthroughs in basic and clinical biomedical science, with the goal of advancing the field of medicine. With an impressive Impact Factor of 15.9 in 2022, it is recognized as one of the leading journals in the "Medicine, Research & Experimental" category of the Web of Science. The journal attracts a diverse readership from various medical disciplines and sectors. It publishes a wide range of research articles encompassing all biomedical specialties, including Autoimmunity, Gastroenterology, Immunology, Metabolism, Nephrology, Neuroscience, Oncology, Pulmonology, Vascular Biology, and many others. The Editorial Board consists of esteemed academic editors who possess extensive expertise in their respective fields. They are actively involved in research, ensuring the journal's high standards of publication and scientific rigor.
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