Human Endogenous Retrovirus-K and TDP-43 Expression Bridges ALS and HIV Neuropathology.

Human Endogenous Retrovirus-K and TDP-43 Expression Bridges ALS and HIV Neuropathology.
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DOI:
10.3389/fmicb.2017.01986
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发表时间:
2017
影响因子:
5.2
通讯作者:
Nath A
Nath A
中科院分区:
生物学2区
文献类型:
--
作者:
Douville RN;Nath A

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尽管内源性逆转录病毒在人类疾病中存在反复关联,但其病理作用背后的机制仍有待解决。在这里,我们讨论了人类内源性逆转录病毒K(Herv-K)在人类免疫缺陷病毒(HIV)感染个体中的表达是HIV相关神经系统疾病(如HIV脑炎和HIV相关神经认知障碍)的一个独特的病理方面。在大多数HIV感染者中观察到神经元Herv-K水平的增强,以HIV复制为标志的脑组织中的HERV-K水平更高。此外,我们强调了肌萎缩侧索硬化症和HIV脑炎之间一个重要的神经病理重叠,那就是在神经元中形成神经毒性TDP-43沉积。在这里,我们主张加强ERV生物学领域的跨学科研究,以HERV-K表达如何在HIV神经病理学中具有新的机制和治疗意义为例。
Despite the repetitive association of endogenous retroviruses in human disease, the mechanisms behind their pathological contributions remain to be resolved. Here we discuss how neuronal human endogenous retrovirus-K (HERV-K) expression in human immunodeficiency virus (HIV)-infected individuals is a distinct pathological aspect of HIV-associated neurological conditions, such as HIV encephalitis and HIV-associated neurocognitive disorders. Enhanced neuronal HERV-K levels were observed in the majority of HIV-infected individuals, and to a higher degree in brain tissue marked by HIV replication. Moreover, we highlight an important neuropathological overlap between amyotrophic lateral sclerosis and HIV encephalitis, that being the formation of neurotoxic TDP-43 deposits in neurons. Herein, we argue for enhanced transdisciplinary research in the field of ERV biology, using an example of how HERV-K expression has novel mechanistic and therapeutic implications for HIV neuropathology.
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