An Aquareovirus Exploits Membrane-Anchored HSP70 To Promote Viral Entry

文献类型： 外文期刊

第一作者： Hou, Guoli

作者： Hou, Guoli;Zhang, Yong-An;Hou, Guoli;Zhang, Qiushi;Li, Chun;Ding, Geye;Hu, Lingling;Chen, Xiaoying;Lv, Zhao;Xiao, Tiaoyi;Li, Junhua;Fan, Yuding;Zou, Jun

作者机构：

关键词： temperature dependent; viral entry; GCRV; HSP70; VP7

期刊名称：MICROBIOLOGY SPECTRUM （ 影响因子：3.7； 五年影响因子：5.9 ）

ISSN： 2165-0497

年卷期： 2023 年 11 卷 3 期

页码：

收录情况： SCI

摘要： The seasonality of viral diseases in ectotherms is a prevailing phenomenon in the aquatic environment, which causes huge economic losses every year worldwide and hinders sustainable development of the aquaculture industry. Nevertheless, our understanding of the molecular mechanism of how temperature determines the pathogenesis of aquatic viruses remains largely unexplored. Temperature dependency of viral diseases in ectotherms has been an important scientific issue for decades, while the molecular mechanism behind this phenomenon remains largely mysterious. In this study, deploying infection with grass carp reovirus (GCRV), a double-stranded RNA aquareovirus, as a model system, we demonstrated that the cross talk between HSP70 and outer capsid protein VP7 of GCRV determines temperature-dependent viral entry. Multitranscriptomic analysis identified HSP70 as a key player in the temperature-dependent pathogenesis of GCRV infection. Further biochemical, small interfering RNA (siRNA) knockdown, pharmacological inhibition, and microscopic approaches revealed that the primary plasma membrane-anchored HSP70 interacts with VP7 to facilitate viral entry during the early phase of GCRV infection. Moreover, VP7 functions as a key coordinator protein to interact with multiple housekeeping proteins and regulate receptor gene expression, concomitantly facilitating viral entry. This work illuminates a previously unidentified immune evasion mechanism by which an aquatic virus hijacks heat shock response-related proteins to enhance viral entry, pinpointing targeted preventives and therapeutics for aquatic viral diseases.IMPORTANCE The seasonality of viral diseases in ectotherms is a prevailing phenomenon in the aquatic environment, which causes huge economic losses every year worldwide and hinders sustainable development of the aquaculture industry. Nevertheless, our understanding of the molecular mechanism of how temperature determines the pathogenesis of aquatic viruses remains largely unexplored. In this study, by deploying grass carp reovirus (GCRV) infection as a model system, we demonstrated that temperature-dependent, primarily membrane-localized HSP70 interacts with major outer capsid protein VP7 of GCRV to bridge the virus-host interaction, reshape the host's behaviors, and concomitantly facilitate viral entry. Our work unveils a central role of HSP70 in the temperature-dependent pathogenesis of aquatic viruses and provides a theoretical basis for the formulation of prevention and control strategies for aquatic viral diseases.

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