Animal models for studies of HIV-1 brain reservoirs.
Animal models for studies of HIV-1 brain reservoirs.
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DOI：
10.1002/jlb.5vmr0322-161r
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发表时间：
2022-11
影响因子：
5.5
通讯作者：
Dash, Prasanta K.
中科院分区：
文献类型：
--
作者：
Waight, Emiko;Zhang, Chen;Mathews, Saumi;Kevadiya, Bhavesh D.;Lloyd, K. C. Kent;Gendelman, Howard E.;Gorantla, Santhi;Poluektova, Larisa Y.;Dash, Prasanta K.
HIV-1通常逃避强大的抗逆转录病毒介导的免疫应答，导致包括CNS在内的解剖学特权部位的持续感染。在CD 4 + T细胞和单核吞噬细胞（MP;单核细胞、巨噬细胞、小胶质细胞和树突状细胞）中存在有效抗逆转录病毒治疗（ART）的情况下发生持续低水平感染。在中枢神经系统内，生产性病毒感染仅见于小胶质细胞和脑膜、血管周围和脉络膜巨噬细胞。MP作为主要的病毒CNS储库。已经开发了动物模型来重现自然的人类HIV-1感染。这些包括非人灵长类动物、人源化小鼠、EcoHIV和转基因啮齿动物模型。这些模型已用于研究疾病病理生物学、抗逆转录病毒和免疫调节剂、病毒储存库和根除策略。然而，这些模型中的每一个都限于人类疾病的特定组成部分。事实上，HIV-1物种特异性必须推动治疗和治愈研究。这些已经在反映潜伏感染的几个模型系统中进行了研究，特别是在MP（骨髓、单核细胞、巨噬细胞、小胶质细胞和组织细胞）群体中。因此，需要额外的小动物模型，允许生产性病毒复制，以使病毒携带进入大脑和病毒易感MP。为此，本综述概述了目前可用于研究髓系脑储库的动物模型，并强调了缺乏和需要未来研究的领域，以更有效地研究疾病特异性事件，这些事件可能对CNS内外的病毒根除研究有用。综述了最近的啮齿动物模型，含有人类骨髓和T细胞的未来治疗和病毒消除研究中枢神经系统。
The HIV‐1 often evades a robust antiretroviral‐mediated immune response, leading to persistent infection within anatomically privileged sites including the CNS. Continuous low‐level infection occurs in the presence of effective antiretroviral therapy (ART) in CD4+ T cells and mononuclear phagocytes (MP; monocytes, macrophages, microglia, and dendritic cells). Within the CNS, productive viral infection is found exclusively in microglia and meningeal, perivascular, and choroidal macrophages. MPs serve as the principal viral CNS reservoir. Animal models have been developed to recapitulate natural human HIV‐1 infection. These include nonhuman primates, humanized mice, EcoHIV, and transgenic rodent models. These models have been used to study disease pathobiology, antiretroviral and immune modulatory agents, viral reservoirs, and eradication strategies. However, each of these models are limited to specific component(s) of human disease. Indeed, HIV‐1 species specificity must drive therapeutic and cure studies. These have been studied in several model systems reflective of latent infections, specifically in MP (myeloid, monocyte, macrophages, microglia, and histiocyte cell) populations. Therefore, additional small animal models that allow productive viral replication to enable viral carriage into the brain and the virus‐susceptible MPs are needed. To this end, this review serves to outline animal models currently available to study myeloid brain reservoirs and highlight areas that are lacking and require future research to more effectively study disease‐specific events that could be useful for viral eradication studies both in and outside the CNS. Review on recent rodent models that contain both human myeloid and T cells for future therapeutics and viral elimination investigations in CNS.
影响因子：
6.2
作者：
Gorantla, Santhi;Gendelman, Howard E.;Poluektova, Larisa Y.
通讯作者：
Poluektova, Larisa Y.