Transmitted/founder SHIV.D replicates in the brain, causes neuropathogenesis, and persists on combination antiretroviral therapy in rhesus macaques.

IF 2.7 3区医学 Q3 VIROLOGY

Retrovirology Pub Date : 2023-08-10 DOI:10.1186/s12977-023-00628-5

Rachel M Podgorski, Jake A Robinson, Mandy D Smith, Suvadip Mallick, Huaqing Zhao, Ronald S Veazey, Dennis L Kolson, Katharine J Bar, Tricia H Burdo

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引用次数: 0

Abstract

A biologically relevant non-human primate (NHP) model of HIV persistence in the central nervous system (CNS) is necessary. Most current NHP/SIV models of HIV infection fail to recapitulate viral persistence in the CNS without encephalitis or fail to employ viruses that authentically represent the ongoing HIV-1 pandemic. Here, we demonstrate viral replication in the brain and neuropathogenesis after combination antiretroviral therapy (ART) in rhesus macaques (RMs) using novel macrophage-tropic transmitted/founder (TF) simian-human immunodeficiency virus SHIV.D.191,859 (SHIV.D). Quantitative immunohistochemistry (IHC) and DNA/RNAscope in situ hybridization (ISH) were performed on three brain regions from six SHIV.D-infected RMs; two necropsied while viremic, two during analytical treatment interruptions, and two on suppressive ART. We demonstrated myeloid-mediated neuroinflammation, viral replication, and proviral DNA in the brain in all animals. These results demonstrate that TF SHIV.D models native HIV-1 CNS replication, pathogenesis, and persistence on ART in rhesus macaques.

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在恒河猴中，传播/创始人SHIV.D在大脑中复制，引起神经病变，并在联合抗逆转录病毒治疗中持续存在。

有必要建立一种与生物学相关的非人类灵长类动物（NHP）的中枢神经系统（CNS）HIV持久性模型。目前大多数HIV感染的NHP/SIV模型未能在没有脑炎的情况下重现病毒在中枢神经系统中的持久性，或者未能使用真正代表正在进行的HIV-1大流行的病毒。在这里，我们证明了在恒河猴（RM）中使用新型嗜巨噬细胞传播/创始人（TF）猴人类免疫缺陷病毒SHIV进行联合抗逆转录病毒治疗（ART）后，病毒在大脑中的复制和神经发生。D.191859（SHIV.D）。对6个SHIV的3个脑区进行定量免疫组织化学（IHC）和DNA/RNAscope原位杂交（ISH）。D-感染RM；两只在病毒血症时坏死，两只在分析治疗中断时坏死，还有两只在抑制性ART中坏死。我们在所有动物的大脑中证明了髓系介导的神经炎症、病毒复制和前病毒DNA。这些结果表明TF SHIV。D模拟恒河猴体内HIV-1中枢神经系统的复制、发病机制和抗逆转录病毒疗法的持久性。

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来源期刊

Retrovirology 医学-病毒学

CiteScore

5.80

自引率

3.00%

发文量

审稿时长

>0 weeks

期刊介绍： Retrovirology is an open access, online journal that publishes stringently peer-reviewed, high-impact articles on host-pathogen interactions, fundamental mechanisms of replication, immune defenses, animal models, and clinical science relating to retroviruses. Retroviruses are pleiotropically found in animals. Well-described examples include avian, murine and primate retroviruses. Two human retroviruses are especially important pathogens. These are the human immunodeficiency virus, HIV, and the human T-cell leukemia virus, HTLV. HIV causes AIDS while HTLV-1 is the etiological agent for adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. Retrovirology aims to cover comprehensively all aspects of human and animal retrovirus research.