Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
J Integr Neurosci. 2024 Sep 19;23(9):172. doi: 10.31083/j.jin2309172.
Infection of astrocytes by Human Immunodeficiency Virus (HIV-1) remains a topic of debate, with conflicting data, yet instances of astrocytes containing viral DNA have been observed . In this study, we aimed to elucidate potential routes through which astrocytes could be infected and their ability to produce infectious particles using primary human astrocytes.
We infected primary astrocytes derived from either neuroprogenitor cells (NPCs) or induced pluripotent stem cells (iPSCs) that express both C-X-C chemokine receptor type 4 (CXCR4) and the C-C chemokine receptor type 5 (CCR5) coreceptors, using either cell-free HIV-1 virus directly or cell-associated virus indirectly through infected macrophages and microglia.
Low-level infectivity by cell-free viruses was primarily attributed to a defect in the entry process. Bypassing HIV-specific receptor-mediated entry using pseudotyped viruses resulted in productive infection and the release of infectious particles.
These findings suggest that astrocytes may be one of the potential sources of neurotoxicity in HIV-associated neurocognitive disorders (HAND) and could possibly act as reservoirs for HIV in the central nervous system (CNS).
人类免疫缺陷病毒（HIV-1）感染星形胶质细胞仍然是一个有争议的话题，存在相互矛盾的数据，但已经观察到星形胶质细胞中含有病毒 DNA。在这项研究中，我们旨在阐明星形胶质细胞可能被感染的潜在途径，以及它们使用原代人星形胶质细胞产生感染性颗粒的能力。
我们使用来自神经祖细胞（NPC）或诱导多能干细胞（iPSC）的原代星形胶质细胞进行感染，这些细胞表达 C-X-C 趋化因子受体 4（CXCR4）和 C-C 趋化因子受体 5（CCR5）核心受体，使用无细胞 HIV-1 病毒直接感染，或通过感染的巨噬细胞和小胶质细胞间接感染细胞相关病毒。
低水平的无细胞病毒感染主要归因于进入过程中的缺陷。使用假型病毒绕过 HIV 特异性受体介导的进入，导致产生感染和释放感染性颗粒。
这些发现表明星形胶质细胞可能是 HIV 相关神经认知障碍（HAND）中神经毒性的潜在来源之一，并且可能在中枢神经系统（CNS）中充当 HIV 的储库。
