未折叠蛋白反应的药理学调控：针对基孔肯雅病毒的潜在抗病毒策略
Pharmacological Manipulation of UPR: Potential Antiviral Strategy Against Chikungunya Virus.
作者信息
Agrawal Nishtha, Saini Sanjesh, Khanna Madhu, Dhawan Gagan, Dhawan Uma
机构信息
Department of Virology (a Unit of Department of Microbiology), Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, 110007 India.
Department of Biomedical Science, Acharya Narendra Dev College, University of Delhi, Kalkaji, New Delhi, 110019 India.
出版信息
Indian J Microbiol. 2022 Dec;62(4):634-640. doi: 10.1007/s12088-022-01046-5. Epub 2022 Nov 1.
ABSTRACT
Viruses invade the host cells and maneuver the cellular translation machinery to translate the viral proteins in substantial amounts, which may disturb Endoplasmic Reticulum homeostasis leading to induction of Unfolded Protein Response (UPR), a host response pathway involved in viral pathogenesis. Here, we investigated the effect of UPR pathways on the pathogenesis of chikungunya virus infection. We observed that chikungunya virus mediated the modulation of UPR. A positive modulation was observed in the activation of IRE1 and ATF6 branch while the PERK branch of UPR observed suppressed upon virus infection. We further investigated the effect of the inhibition of UPR pathways on chikungunya virus replication using inhibitors for each branch. Cells treated with 3-ethoxy-5,6-dibromosalicylaldehyde (IRE1 inhibitor) and AEBSF (ATF6 inhibitor) significantly inhibits the viral replication process. This study has provided a novel perspective in designing antivirals against chikungunya virus.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s12088-022-01046-5.
摘要
病毒侵入宿主细胞并操纵细胞翻译机制大量翻译病毒蛋白，这可能会扰乱内质网稳态，从而引发未折叠蛋白反应（UPR），这是一种参与病毒发病机制的宿主反应途径。在此，我们研究了UPR途径对基孔肯雅病毒感染发病机制的影响。我们观察到基孔肯雅病毒介导了UPR的调节。在IRE1和ATF6分支的激活中观察到正向调节，而在病毒感染后观察到UPR的PERK分支受到抑制。我们进一步使用针对每个分支的抑制剂研究了UPR途径抑制对基孔肯雅病毒复制的影响。用3-乙氧基-5,6-二溴水杨醛（IRE1抑制剂）和AEBSF（ATF6抑制剂）处理的细胞显著抑制了病毒复制过程。这项研究为设计针对基孔肯雅病毒的抗病毒药物提供了新的视角。
补充信息
在线版本包含可在10.1007/s12088-022-01046-5获取的补充材料。
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