Computational analysis of human host binding partners of chikungunya and dengue viruses during coinfection.

IF 2.7 4区 医学 Q3 IMMUNOLOGY
Ritu Ghildiyal, Reema Gabrani
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引用次数: 1

Abstract

Mosquito-borne viral diseases like chikungunya and dengue infections can cause severe illness and have become major public health concerns. Chikungunya virus (CHIKV) and dengue virus (DENV) infections share similar primary clinical manifestations and are transmitted by the same vector. Thus, the probability of their coinfection gets increased with more severe clinical complications in the patients. The present study was undertaken to elucidate the common human interacting partners of CHIKV and DENV proteins during coinfection. The viral-host protein-protein interactome was constructed using Cytoscape. Subsequently, significant host interactors were identified during coinfection. The network analysis elucidated 57 human proteins interacting with both CHIKV and DENV, represented as hub-bottlenecks. The functional and biological analyses of the 40 hub-bottlenecks revealed that they are associated with phosphoinositide 3-kinases (PI3K)/AKT, p53 signaling pathways, regulation of cell cycle and apoptosis during coinfection. Moreover, the molecular docking analysis uncovered the tight and robust binding of selected hub-bottlenecks with CHIKV/DENV proteins. Additionally, 23 hub-bottlenecks were predicted as druggable candidates that could be targeted to eradicate the host-viral interactions. The elucidated common host binding partners during DENV and CHIKV coinfection as well as indicated approved drugs can support the therapeutics development.

基孔肯雅病毒和登革热病毒合并感染时人类宿主结合伴侣的计算分析。
基孔肯雅热和登革热等蚊媒病毒性疾病可导致严重疾病,并已成为主要的公共卫生问题。基孔肯雅病毒(CHIKV)和登革热病毒(DENV)感染具有相似的主要临床表现,并由同一媒介传播。因此,合并感染的概率增加,患者的临床并发症更严重。本研究旨在阐明CHIKV和DENV蛋白在共同感染过程中共同的人类相互作用伙伴。利用Cytoscape构建了病毒-宿主蛋白-蛋白相互作用组。随后,在共同感染期间确定了重要的宿主相互作用物。网络分析阐明了57种与CHIKV和DENV相互作用的人类蛋白,它们被表示为枢纽瓶颈。对40个中心瓶颈的功能和生物学分析表明,它们与磷酸肌肽3-激酶(PI3K)/AKT、p53信号通路、共感染过程中细胞周期和凋亡的调节有关。此外,分子对接分析揭示了所选枢纽瓶颈与CHIKV/DENV蛋白的紧密和稳健结合。此外,23个中心瓶颈被预测为可用于消除宿主-病毒相互作用的候选药物。在DENV和CHIKV共感染过程中所阐明的共同宿主结合伙伴以及指示批准的药物可以支持治疗方法的开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Pathogens and disease
Pathogens and disease IMMUNOLOGY-INFECTIOUS DISEASES
CiteScore
7.40
自引率
3.00%
发文量
44
期刊介绍: Pathogens and Disease publishes outstanding primary research on hypothesis- and discovery-driven studies on pathogens, host-pathogen interactions, host response to infection and their molecular and cellular correlates. It covers all pathogens – eukaryotes, prokaryotes, and viruses – and includes zoonotic pathogens and experimental translational applications.
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