Enigma of HIV-1 latent infection in astrocytes: an in-vitro study using protein kinase C agonist as a latency reversing agent.
Enigma of HIV-1 latent infection in astrocytes: an in-vitro study using protein kinase C agonist as a latency reversing agent.
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DOI：
10.1016/j.micinf.2015.05.006
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发表时间：
2015-09
影响因子：
5.8
通讯作者：
Chauhan A
中科院分区：
文献类型：
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作者：
Chauhan A
清除HIV-1以治愈接受抑制性抗逆转录病毒治疗的患者的感染需要针对所有可能的病毒宿主。除了记忆性CD 4 + T细胞外，还发现了其他几种HIV-1储库。HIV-1感染在大脑中作为一个水库是有据可查的，但没有充分的特点。在那里，小胶质细胞、血管周围巨噬细胞和星形胶质细胞可以被HIV-1感染。星形胶质细胞中的HIV-1感染被描述为非生产性的，主要是潜伏性感染。使用原代人星形胶质细胞，我们研究了潜伏的HIV-1感染，并测试了佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA），一种蛋白激酶C激动剂，作为HIV-1潜伏期逆转剂在感染的星形胶质细胞中的作用。氯喹（CQ）用于促进初始HIV-1从星形胶质细胞内体逃逸。CQ显著增加HIV-1感染。但是用PMA或病毒达特蛋白处理与未经处理的HIV-1感染的星形胶质细胞相似。对VSV包膜假型HIV-1感染的星形胶质细胞的长期随访显示持续感染110天，表明病毒处于活跃状态。
Purging HIV-1 to cure the infection in patients undergoing suppressive antiretroviral therapy requires targeting all possible viral reservoirs. Other than the memory CD4+ T cells, several other HIV-1 reservoirs have been identified. HIV-1 infection in the brain as a reservoir is well documented, but not fully characterized. There, microglia, perivascular macrophages, and astrocytes can be infected by HIV-1. HIV-1 infection in astrocytes has been described as a nonproductive and primarily a latent infection. Using primary human astrocytes, we investigated latent HIV-1 infection and tested phorbol 12-myristate 13-acetate (PMA), a protein kinase C agonist, as an HIV-1-latency- reversing agent in infected astrocytes. Chloroquine (CQ) was used to facilitate initial HIV-1 escape from endosomes in astrocytes. CQ significantly increased HIV-1 infection. But treatment with PMA or viral Tat protein was similar to untreated HIV-1-infected astrocytes. Long-term follow-up of VSV-envelope-pseudotyped HIV-1 infected astrocytes showed persistent infection for 110 days, indicating the active state of the virus.