Brain macrophages harbor latent, infectious simian immunodeficiency virus
Brain macrophages harbor latent, infectious simian immunodeficiency virus
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DOI：
10.1097/qad.0000000000002269
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发表时间：
2019-12-01
期刊：
影响因子：
3.8
通讯作者：
Clements, Janice E.
中科院分区：
文献类型：
--
作者：
Abreu, Celina;Shirk, Erin N.;Clements, Janice E.
目前的审查审查的作用，脑巨噬细胞，即血管周围的巨噬细胞和小胶质细胞，作为一个潜在的病毒水库抗逆转录病毒治疗（ART）治疗，猴免疫缺陷病毒（SIV）感染的猕猴。在ART抑制期间，HIV和SIV在中枢神经系统中的潜在病毒储库的作用（如果有的话）是一个尚未解决的问题。HIV和SIV在急性和慢性感染期间感染血液和组织中的CD4（+）淋巴细胞和髓样细胞。在急性感染期间，通过活化的CD4（+）淋巴细胞和单核细胞从血液中浸润，HIV传播到大脑，并在胚胎来源的常驻小胶质细胞和单核细胞来源的血管周围巨噬细胞中建立。ART控制HIV感染者外周血和脑脊液中的病毒复制，但不直接消除血液、组织或大脑中的感染细胞。血液和淋巴组织中潜伏感染的静息CD4（+）淋巴细胞是公认的病毒储库，一旦停止抗逆转录病毒治疗，就会反弹。相比之下，中枢神经系统驻留的小胶质细胞和脑中的血管周围巨噬细胞尚未被检查为在抑制性ART期间HIV的潜在储库。组织中的巨噬细胞是在诸如肠、肺、脾、淋巴结和脑的组织中被HIV和SIV感染的长寿命细胞，并且有助于组织中的持续炎症。然而，它们在病毒持久性和潜伏期中的潜在作用或它们在缺乏ART的情况下反弹的潜力尚未被研究。已经表明，通过HIV DNA PCR在CD4（+）淋巴细胞中测量HIV潜伏期高估了导致反弹的HIV潜伏库的大小，所述HIV潜伏库是含有复制病毒基因组的细胞。因此，定量病毒生长试验已被用作携带感染性病毒DNA的潜伏细胞数量的可靠测量，并可能构成功能性潜伏库。使用专门设计用于定量SIV猕猴模型中潜伏感染的CD4（+）淋巴细胞和髓样细胞的定量病毒生长测定，我们证明脑中的巨噬细胞携带SIV基因组，在该测定中重新激活并产生感染性病毒，证明这些细胞具有成为储库的潜力。
The current review examines the role of brain macrophages, that is perivascular macrophages and microglia, as a potential viral reservoir in antiretroviral therapy (ART) treated, simian immunodeficiency virus (SIV)-infected macaques. The role, if any, of latent viral reservoirs of HIV and SIV in the central nervous system during ART suppression is an unresolved issue. HIV and SIV infect both CD4(+) lymphocytes and myeloid cells in blood and tissues during acute and chronic infection. HIV spread to the brain occurs during acute infection by the infiltration of activated CD4(+) lymphocytes and monocytes from blood and is established in both embryonically derived resident microglia and monocyte-derived perivascular macrophages. ART controls viral replication in peripheral blood and cerebrospinal fluid in HIV-infected individuals but does not directly eliminate infected cells in blood, tissues or brain. Latently infected resting CD4(+) lymphocytes in blood and lymphoid tissues are a well recognized viral reservoir that can rebound once ART is withdrawn. In contrast, central nervous system resident microglia and perivascular macrophages in brain have not been examined as potential reservoirs for HIV during suppressive ART. Macrophages in tissues are long-lived cells that are HIV and SIV infected in tissues such as gut, lung, spleen, lymph node and brain and contribute to ongoing inflammation in tissues. However, their potential role in viral persistence and latency or their potential to rebound in the absence ART has not been examined. It has been shown that measurement of HIV latency by HIV DNA PCR in CD4(+) lymphocytes overestimates the size of the latent reservoirs of HIV that contribute to rebound that is cells containing the genomes of replicative viruses. Thus, the quantitative viral outgrowth assay has been used as a reliable measure of the number of latent cells that harbor infectious viral DNA and, may constitute a functional latent reservoir. Using quantitative viral outgrowth assays specifically designed to quantitate latently infected CD4(+) lymphocytes and myeloid cells in an SIV macaque model, we demonstrated that macrophages in brain harbor SIV genomes that reactivate and produce infectious virus in this assay, demonstrating that these cells have the potential to be a reservoir.