Human endogenous retrovirus-K(II) envelope induction protects neurons during HIV/AIDS.
Human endogenous retrovirus-K(II) envelope induction protects neurons during HIV/AIDS.
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人内源性逆转录病毒-K（II）包膜诱导在HIV/AIDS期间保护神经元。
DOI：
10.1371/journal.pone.0097984
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Power C
中科院分区：
文献类型：
--
作者：
Bhat RK;Rudnick W;Antony JM;Maingat F;Ellestad KK;Wheatley BM;Tönjes RR;Power C
人内源性逆转录病毒（HERVs）的表达因细胞类型和生理环境而异。尽管其表达的功能后果仍不清楚，但HERV-K已与多种疾病的发病机制有关。人类免疫缺陷病毒（HIV）感染引起神经炎症，神经元损伤和死亡。在此，我们研究HERV-K（II）/（HML-2）包膜（Env）的表达及其在HIV/AIDS过程中在脑中的作用。通过真实的时间RT-PCR、大规模平行（深度）测序、免疫印迹和免疫组织化学，评估了健康脑组织、尸检HIV HIV感染（HIV+）和未感染（HIV−）脑组织以及神经细胞培养物中HERV-K（II）Env的表达。在宿主反应测定中分析表达HERV-K（II）Env的神经元和神经干细胞，包括细胞活力、免疫反应和神经行为结果。人脑转录组的深度测序揭示了由HERV-K编码的RNA序列是在人脑中检测到的最丰富的HERV序列之一。不同细胞类型的比较显示，HERV-K（II）env RNA丰度在培养的人类神经元中最高，但受到表皮生长因子暴露的抑制。HERV-K（II）Env免疫反应性在HIV/AIDS患者的大脑皮层中增加，主要位于神经元中。用HERV-K（II）Env转染的人神经元细胞表现出增加的NGF和BDNF表达。HERV-K（II）Env在神经元细胞中的表达增加了细胞活力，并防止了HIV-1 Vpr介导的神经毒性。脑内递送由神经干细胞表达的HERV-K（II）Env抑制TNF-α表达和小胶质细胞活化，同时还改善vpr/RAG 1 −/−小鼠的神经行为缺陷。HERV-K（II）Env在人类神经元中高度表达，特别是在HIV/AIDS期间，但另外还发挥神经保护作用。这些发现意味着HERV基因产物可能在病理生理应激的情况下发挥适应性作用，这可能是人类基因组中HERV保守性的基础。
Human endogenous retroviruses (HERVs) are differentially expressed depending on the cell type and physiological circumstances. HERV-K has been implicated in the pathogenesis of several diseases although the functional consequences of its expression remain unknown. Human immunodeficiency virus (HIV) infection causes neuroinflammation with neuronal damage and death. Herein, we investigated HERV-K(II)/(HML-2) envelope (Env) expression and its actions in the brain during HIV/AIDS. HERV-K(II) Env expression was assessed in healthy brain tissues, autopsied HIV HIV− infected (HIV+) and uninfected (HIV−) brains and in neural cell cultures by real time RT-PCR, massively parallel (deep) sequencing, immunoblotting and immunohistochemistry. Neuronal and neural stem cells expressing HERV-K(II) Env were analyzed in assays of host responses including cellular viability, immune responses and neurobehavioral outcomes. Deep sequencing of human brain transcriptomes disclosed that RNA sequences encoded by HERV-K were among the most abundant HERV sequences detected in human brain. Comparison of different cell types revealed that HERV-K(II) env RNA abundance was highest in cultured human neurons but was suppressed by epidermal growth factor exposure. HERV-K(II) Env immunoreactivity was increased in the cerebral cortex from persons with HIV/AIDS, principally localized in neurons. Human neuronal cells transfected with HERV-K(II) Env exhibited increased NGF and BDNF expression. Expression of HERV-K(II) Env in neuronal cells increased cellular viability and prevented neurotoxicity mediated by HIV-1 Vpr. Intracerebral delivery of HERV-K(II) Env expressed by neural stem cells suppressed TNF-α expression and microglial activation while also improving neurobehavioral deficits in vpr/RAG1−/− mice. HERV-K(II) Env was highly expressed in human neurons, especially during HIV/AIDS, but in addition exerted neuroprotective effects. These findings imply that HERV gene products might exert adaptive effects in circumstances of pathophysiological stress, perhaps underlying the conservation of HERVs within the human genome.
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影响因子：
3.7
作者：
Bhat RK;Ellestad KK;Wheatley BM;Warren R;Holt RA;Power C
通讯作者：
Power C
影响因子：
25
作者：
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Power, C
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11.2
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影响因子：
4.8
作者：
Acharjee, Shaona;Noorbakhsh, Farshid;Power, Christopher
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Power, Christopher
影响因子：
5.3
作者：
Frendo, JL;Olivier, D;Mallet, F
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Mallet, F