When do models of NeuroAIDS faithfully imitate "the real thing"?
When do models of NeuroAIDS faithfully imitate "the real thing"?
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DOI：
10.1007/s13365-017-0601-5
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发表时间：
2018-04
影响因子：
3.2
通讯作者：
Kolson D
中科院分区：
文献类型：
--
作者：
Gelman BB;Endsley J;Kolson D
接受抗逆转录病毒药物治疗的艾滋病毒感染者仍然面临神经系统方面的挑战。HIV相关的神经认知障碍（HAND）可能发生，潜伏的病毒DNA持续存在于中枢神经系统（CNS）中，阻碍了HIV的根除。这次交流的重点是如何开发HAND和CNS HIV潜伏期的实验模型，以最好地模仿患病人类的CNS病理生理，我们认为这是“真实的东西”。具有活跃中枢神经系统病毒复制的HIV脑炎（HIVE）模型是在艾滋病流行的早期开发的。这些模型的临床相关性正在急剧下降，因为HIVE很少发生在病毒抑制的患者中，而HAND仍然很常见。寻找改进的HAND模型应结合病毒抑制患者的神经化学、神经免疫学和神经病理学特征。尸检脑组织标本证实，这些患者常见的异常包括脑内皮细胞活化和突触传递的神经化学失衡；经典的神经退行性变可能没有那么重要。关于病毒抑制的潜伏性HIV，人脑标本显示，中枢神经系统中潜伏性HIV前病毒DNA库相对于整个身体库相对较小，并且多年来没有实质性变化。中枢神经系统的潜伏病毒池可能不同于淋巴组织，因为单核吞噬细胞系统维持生产性感染（相对于淋巴细胞）。病毒抑制患者的人类中枢神经系统的这些和有待发现的方面需要在实验模型中得到更好的定义和解决。为了保持临床相关性，HAND和病毒潜伏期的模型应该忠实地模拟“真实的东西”。
HIV-infected patients treated with antiretroviral medicines (ART) still face neurological challenges. HIV-associated neurocognitive disturbances (HAND) can occur, and latent viral DNA persisting in the central nervous system (CNS) prevents eradication of HIV. This communication focuses on how to develop experimental models of HAND and CNS HIV latency that best imitate the CNS pathophysiology in diseased humans, which we take to be “the real thing.” Models of HIV encephalitis (HIVE) with active CNS viral replication were developed in the early years of the AIDS pandemic. The clinical relevancy of such models is in sharp decline because HIVE seldom occurs in virally suppressed patients, while HAND remains common. The search for improved models of HAND should incorporate the neurochemical, neuroimmunological and neuropathological features of virally suppressed patients. Common anomalies in these patients as established in autopsy brain specimens include brain endothelial cell activation and neurochemical imbalances of synaptic transmission; classical neurodegeneration may not be as crucial. With regard to latent HIV with viral suppression, human brain specimens show that the pool of latent proviral HIV DNA in the CNS is relatively small relative to the total body pool and does not change substantially over years. The CNS pool of latent virus probably differs from lymphoid tissues, because the mononuclear phagocyte system sustains productive infection (versus lymphocytes). These and yet-to-be discovered aspects of the human CNS of virally suppressed patients need to be better defined and addressed in experimental models. To maintain clinical relevancy, models of HAND and viral latency should faithfully emulate “the real thing.”
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影响因子：
11.2
作者：
Ellis, RJ;Hsia, K;Dupont, R
通讯作者：
Dupont, R
影响因子：
32.4
作者：
Calantone, Nina;Wu, Fan;Brenchley, Jason M.
通讯作者：
Brenchley, Jason M.
DOI：
10.1007/s11481-016-9652-2
发表时间：
2016-06
期刊：
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
影响因子：
--
作者：
Buzhdygan T;Lisinicchia J;Patel V;Johnson K;Neugebauer V;Paessler S;Jennings K;Gelman B
通讯作者：
Gelman B
影响因子：
6.2
作者：
Gelman, Benjamin B.;Lisinicchia, Joshua G.;Chen, Tianshen;Johnson, Kenneth M.;Jennings, Kristofer;Freeman, Daniel H., Jr.;Soukup, Vicki M.
通讯作者：
Soukup, Vicki M.
抑制性抗逆转录病毒疗法的手神经病理学：重新考虑脑炎和神经变性。
影响因子：
4.6
作者：
Gelman, Benjamin B.
通讯作者：
Gelman, Benjamin B.