Cellular reservoirs of HIV-1 in the central nervous system of infected individuals: Identification by the combination of in situ polymerase chain reaction and immunohistochemistry
Cellular reservoirs of HIV-1 in the central nervous system of infected individuals: Identification by the combination of in situ polymerase chain reaction and immunohistochemistry
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DOI：
10.1097/00002030-199606000-00002
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发表时间：
1996-06-01
期刊：
影响因子：
3.8
通讯作者：
Pomerantz, RJ
中科院分区：
文献类型：
--
作者：
Bagasra, O;Lavi, E;Pomerantz, RJ
目的：大多数 HIV-1 感染者表现出多种与机会性感染无关的中枢神经系统 (CNS) 疾病，包括艾滋病痴呆综合征、脑炎和各种其他中枢神经系统疾病。本研究旨在评估脑组织中 HIV-1 的细胞储库和表达模式，以进一步了解 HIV-1 神经发病机制。设计：对 22 名 AIDS 患者和 4 名 HIV-1 血清阴性对照尸检获得的 CNS 组织进行分析。方法：结合使用原位 DNA 聚合酶链式反应 (PCR)、逆转录酶 (RT) 启动的原位 PCR 和免疫组织化学对 CNS 样本进行评估。通过利用这种三重染色方法，可以在单细胞水平上鉴定 HIV-1 前病毒 DNA 和 HIV-1 特异性 mRNA。 结果：在所有 22 个 AIDS 脑样本中均检测到 HIV-1，而在 HIV-1 血清阴性个体的 4 个脑样本中均未检测到 HIV-1。艾滋病大脑中最常见的感染细胞是小胶质细胞和巨噬细胞，但中枢神经系统内许多主要组织学细胞类型，包括神经元、微血管内皮细胞 (MVEC) 和星形胶质细胞，都显示出不同水平的 HIV-1 感染。 HIV-1感染细胞的存在并不均匀，感染细胞在整个脑实质中分布不均匀。中枢神经系统中 39-65% 的细胞携带 HIV-1 原病毒，HIV-1 mRNA 表达程度各不相同。脉络丛和 MVEC 表现出相对较高水平的有效感染。结论：这些发现表明，除了小胶质细胞或巨噬细胞之外，中枢神经系统中的几种细胞类型也可能在体内感染 HIV-1，并具有不同水平的 HIV-1 mRNA 表达。中枢神经系统中 HIV-1 的不同细胞库可能与 HIV-1 神经发病机制的分子机制密切相关。此外，MVEC 以及可能的脉络丛细胞的体内感染可能直接导致 HIV-1 穿透血脑屏障。
Objectives: The majority of HIV-1-infected individuals manifest a plethora of central nervous system (CNS) diseases unrelated to opportunistic infections, including AIDS dementia complex, encephalitis, and various other disorders of the CNS. The present study sought to evaluate the cellular reservoirs and expression patterns of HIV-1 in brain tissue to gain further understanding of HIV-1 neuropathogenesis.Design: CNS tissue, obtained post-mortem from 22 patients with AIDS and four HIV-1-seronegative controls, was analyzed.Methods: CNS samples were evaluated using a combination of in situ DNA polymerase chain reaction (PCR), reverse transcriptase (RT)-initiated in situ PCR, and immunohistochemistry. By utilizing this triple-staining methodology, HIV-1 proviral DNA and HIV-1-specific mRNA can be identified at the single cell level.Results: HIV-1 was detected in all 22 AIDS brain specimens and in none of the four brains from HIV-1-seronegative individuals. The most commonly infected cells in AIDS brains were microglia cells and macrophages, but variable levels of HIV-1 infection were demonstrated in many of the major histological cell types within the CNS, including neurons, microvascular endothelial cells (MVEC) and astrocytes. The presence of HIV-1-infected cells was not uniform with infected cells unevenly distributed throughout the brain parenchyma. The degree of HIV-1 mRNA expression varied from 39-65% of the cells in the CNS harboring HIV-1 provirus. Choroid plexus and MVEC exhibited relatively high levels of productive infection.Conclusions: These findings demonstrate that several cell types in the CNS, in addition to microglia or macrophages, may become infected with HIV-1 in vivo with variable levels of HIV-1 mRNA expression. The diverse cellular reservoirs for HIV-1 in the CNS may be critically linked to the molecular mechanisms involved in HIV-1 neuropathogenesis. In addition, in vivo infection of MVEC, and possibly cells in the choroid plexus, may directly contribute to penetration of the blood-brain barrier by HIV-1.