Implication of the Autophagy-Related Protein Beclin1 in the Regulation of EcoHIV Replication and Inflammatory Responses.
Implication of the Autophagy-Related Protein Beclin1 in the Regulation of EcoHIV Replication and Inflammatory Responses.
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DOI：
10.3390/v15091923
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发表时间：
2023-09-14
期刊：
影响因子：
--
通讯作者：
El-Hage N
中科院分区：
文献类型：
--
作者：
Rodriguez M;Owens F;Perry M;Stone N;Soler Y;Almohtadi R;Zhao Y;Batrakova EV;El-Hage N
Beclin 1蛋白（BECN 1，酵母中ATG 6的哺乳动物同源物）在细胞自噬的启动和正常过程中起重要作用。此外，我们和其他人已经证明Beclin 1在病毒复制和先天免疫信号通路中起着重要作用。我们先前使用与甘露糖（Man）缀合的阳离子聚合物聚乙烯亚胺（PEI）作为递送小干扰（si）Beclin 1-PEI-Man纳米复合物的非病毒工具，当鼻内施用给常规小鼠时，其特异性靶向脑中表达甘露糖受体的神经胶质细胞（小神经胶质细胞和星形胶质细胞）。为了扩展我们以前的报告，我们首先使用感染EcoHIV的C57 BL/6 J小鼠，并将其暴露于联合抗逆转录病毒治疗（cART）。我们表明，EcoHIV进入小鼠大脑，而鼻内递送的纳米复合物显着减少了HIV诱导的炎症分子的分泌，并下调转录因子核因子（NF）-kB的表达。由于尽管进行了抑制性抗逆转录病毒治疗，但HIV感染者（PLWH）仍会出现一系列神经认知和运动问题，因此我们随后使用暴露于cART的EcoHIV感染的BECN 1敲除小鼠测量了Beclin 1在运动活动中的作用。与EcoHIV感染的Becn 1 +/+小鼠相比，从EcoHIV感染的Becn 1 +/−小鼠中回收的死后大脑中的病毒复制和细胞因子分泌减少，尽管基于肌肉力量的运动活动的损伤相当。这进一步强调了Beclin 1在调节HIV复制和病毒诱导的细胞因子分泌中的重要性，但在HIV诱导的运动障碍中没有。此外，HIV诱导的运动障碍的原因仍然是推测性的，因为我们表明，这可能不完全是由于病毒载量和/或HIV诱导的炎性细胞因子。
The protein Beclin1 (BECN1, a mammalian homologue of ATG6 in yeast) plays an important role in the initiation and the normal process of autophagy in cells. Moreover, we and others have shown that Beclin1 plays an important role in viral replication and the innate immune signaling pathways. We previously used the cationic polymer polyethyleneimine (PEI) conjugated to mannose (Man) as a non-viral tool for the delivery of a small interfering (si) Beclin1-PEI-Man nanoplex, which specifically targets mannose receptor-expressing glia (microglia and astrocytes) in the brain when administered intranasally to conventional mice. To expand our previous reports, first we used C57BL/6J mice infected with EcoHIV and exposed them to combined antiretroviral therapy (cART). We show that EcoHIV enters the mouse brain, while intranasal delivery of the nanocomplex significantly reduces the secretion of HIV-induced inflammatory molecules and downregulates the expression of the transcription factor nuclear factor (NF)-kB. Since a spectrum of neurocognitive and motor problems can develop in people living with HIV (PLWH) despite suppressive antiretroviral therapy, we subsequently measured the role of Beclin1 in locomotor activities using EcoHIV-infected BECN1 knockout mice exposed to cART. Viral replication and cytokine secretion were reduced in the postmortem brains recovered from EcoHIV-infected Becn1+/− mice when compared to EcoHIV-infected Becn1+/+ mice, although the impairment in locomotor activities based on muscle strength were comparable. This further highlights the importance of Beclin1 in the regulation of HIV replication and in viral-induced cytokine secretion but not in HIV-induced locomotor impairments. Moreover, the cause of HIV-induced locomotor impairments remains speculative, as we show that this may not be entirely due to viral load and/or HIV-induced inflammatory cytokines.
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SERPIN衍生的小肽（SP16）是中枢神经系统细胞中针对HIV诱导的炎症分子和病毒复制的潜在治疗剂。
影响因子：
6
作者：
通讯作者：
--
影响因子：
6.2
作者：
Buch, Shilpa
通讯作者：
Buch, Shilpa
DOI：
10.1007/s11481-018-9788-3
发表时间：
2018-09
期刊：
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
影响因子：
--
作者：
Lapierre J;Rodriguez M;Ojha CR;El-Hage N
通讯作者：
El-Hage N
影响因子：
3.3
作者：
Boven, LA;Middel, J;Nottet, HSLM
通讯作者：
Nottet, HSLM
影响因子：
8.2
作者：
Bhalla, Sonalika;Mehan, Sidharth;Rehman, Muneeb U.
通讯作者：
Rehman, Muneeb U.