Genomic Exploration of the Brain in People Infected with HIV-Recent Progress and the Road Ahead.
Genomic Exploration of the Brain in People Infected with HIV-Recent Progress and the Road Ahead.
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DOI：
10.1007/s11904-023-00675-9
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发表时间：
2023-12
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
成年人的大脑中含有数十亿的小胶质细胞和其他骨髓和淋巴细胞，这些细胞对HIV感染和插入核DNA的逆转录病毒非常敏感。大脑的HIV感染是重要的，因为大脑是一个潜在的大水库网站，可能是HIV治疗策略的障碍，因为感染可能导致HIV相关的神经认知障碍的发展。为了更好地了解中枢神经系统（CNS）的水库和它如何导致神经功能障碍，新的基因组，表观基因组，转录组学和蛋白质组学的方法需要采用。水库的几个特征是重要的学习，包括病毒整合的地方，整合的前病毒是完整的还是有缺陷的，整合的前病毒是否可以从潜伏状态重新激活以播种正在进行的感染，以及这一切如何影响大脑功能。在这里，我们讨论了大脑和血液之间的病毒整合位点的相似性和差异，并讨论了支持和反对这一假设的证据，即在周围没有易感T淋巴细胞的情况下，病毒在受感染的大脑中的住房是不能维持全身感染。此外，来自各种疾病严重程度的HIV +脑的小胶质细胞似乎共享一种类型的共同改变，其由调节突触连接的小胶质细胞基因的表达下调和抑制性染色体区室化定义。因此，大脑的病毒感染，包括在CD4血淋巴细胞水平接近正常的免疫功能正常的情况下，可能与小胶质细胞依赖的神经元支持功能的早期中断有关，导致艾滋病毒感染者的认知和神经功能缺陷。
The adult human brain harbors billions of microglia and other myeloid and lymphoid cells highly susceptible to HIV infection and retroviral insertion into the nuclear DNA. HIV infection of the brain is important because the brain is a potentially large reservoir site that may be a barrier to HIV cure strategies and because infection can lead to the development of HIV-associated neurocognitive disorder. To better understand both the central nervous system (CNS) reservoir and how it can cause neurologic dysfunction, novel genomic, epigenomic, transcriptomic, and proteomic approaches need to be employed. Several characteristics of the reservoir are important to learn, including where the virus integrates, whether integrated proviruses are intact or defective, whether integrated proviruses can be reactivated from a latent state to seed ongoing infection, and how this all impacts brain function. Here, we discuss similarities and differences of viral integration sites between brain and blood and discuss evidence for and against the hypothesis that in the absence of susceptible T-lymphocytes in the periphery, the virus housing in the infected brain is not able to sustain a systemic infection. Moreover, microglia from HIV + brains across a wide range of disease severity appear to share one type of common alteration, which is defined by downregulated expression, and repressive chromosomal compartmentalization, for microglial genes regulating synaptic connectivity. Therefore, viral infection of the brain, including in immunocompetent cases with near-normal levels of CD4 blood lymphocytes, could be associated with an early disruption in microglia-dependent neuronal support functions, contributing to cognitive and neurological deficits in people living with HIV.
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影响因子：
5.5
作者：
Enick PN;Brooker JP;Tumiotto CM;Staines BT;Eron JJ;McMahon DK;Gandhi RT;Mellors JW;Sobolewski MD
通讯作者：
Sobolewski MD
影响因子：
16.6
作者：
Chandrasekaran S;Espeso-Gil S;Loh YE;Javidfar B;Kassim B;Zhu Y;Zhang Y;Dong Y;Bicks LK;Li H;Rajarajan P;Peter CJ;Sun D;Agullo-Pascual E;Iskhakova M;Estill M;Lesch BJ;Shen L;Jiang Y;Akbarian S
通讯作者：
Akbarian S
影响因子：
12.3
作者：
Burren OS;Rubio García A;Javierre BM;Rainbow DB;Cairns J;Cooper NJ;Lambourne JJ;Schofield E;Castro Dopico X;Ferreira RC;Coulson R;Burden F;Rowlston SP;Downes K;Wingett SW;Frontini M;Ouwehand WH;Fraser P;Spivakov M;Todd JA;Wicker LS;Cutler AJ;Wallace C
通讯作者：
Wallace C
影响因子：
3.2
作者：
Hammond, Edward R.;Crum, Rosa M.;Mcarthur, Justin C.
通讯作者：
Mcarthur, Justin C.
DOI：
10.1016/s2352-3018(20)30069-2
发表时间：
2020-05
期刊：
The lancet. HIV
影响因子：
--
作者：
Gupta RK;Peppa D;Hill AL;Gálvez C;Salgado M;Pace M;McCoy LE;Griffith SA;Thornhill J;Alrubayyi A;Huyveneers LEP;Nastouli E;Grant P;Edwards SG;Innes AJ;Frater J;Nijhuis M;Wensing AMJ;Martinez-Picado J;Olavarria E
通讯作者：
Olavarria E