1. An aquatic virus exploits the IL6-STAT3-HSP90 signaling axis to promote viral entry.
- Author
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Hou, Guoli, Lv, Zhao, Liu, Wenzhi, Xiong, Shuting, Zhang, Qiushi, Li, Chun, Wang, Xiaodong, Hu, Liang, Ding, Chunhua, Song, Rui, Wang, Hongquan, Zhang, Yong-An, Xiao, Tiaoyi, and Li, Junhua
- Subjects
HEAT shock proteins ,CYTOSKELETAL proteins ,VIRAL proteins ,CTENOPHARYNGODON idella ,IRIDOVIRUSES ,VIRUS diseases ,HERPESVIRUSES ,ARTIFICIAL membranes - Abstract
Viral seasonality in the aquaculture industry is an important scientific issue for decades. While the molecular mechanisms underpinning the temperature-dependent pathogenesis of aquatic viral diseases remain largely unknown. Here we report that temperature-dependent activation of IL6-STAT3 signaling was exploited by grass carp reovirus (GCRV) to promote viral entry via increasing the expression of heat shock protein 90 (HSP90). Deploying GCRV infection as a model system, we discovered that GCRV induces the IL6-STAT3-HSP90 signaling activation to achieve temperature-dependent viral entry. Further biochemical and microscopic analyses revealed that the major capsid protein VP7 of GCRV interacted with HSP90 and relevant membrane-associated proteins to boost viral entry. Accordingly, exogenous expression of either IL6, HSP90, or VP7 in cells increased GCRV entry in a dose-dependent manner. Interestingly, other viruses (e.g., koi herpesvirus, Rhabdovirus carpio, Chinese giant salamander iridovirus) infecting ectothermic vertebrates have evolved a similar mechanism to promote their infection. This work delineates a molecular mechanism by which an aquatic viral pathogen exploits the host temperature-related immune response to promote its entry and replication, instructing us on new ways to develop targeted preventives and therapeutics for aquaculture viral diseases. Author summary: Viral seasonality in the aquaculture industry has been an important scientific issue for decades, which is causing billions of economic losses every year worldwide. However, there is a lack of understanding of how temperature influences the pathogenesis of aquatic viruses infecting fish, shellfish, and other ectotherms. Here, deploying aquatic grass carp reovirus (GCRV) as a model system, we demonstrate for the first time that the temperature-dependent IL6-STAT3-HSP90 signaling axis is exploited by GCRV to promote viral entry. We found that HSP90 interacted with viral structural proteins and membrane-associated proteins to enable viral entry. Furthermore, our study indicates other aquatic viruses might evolve a similar mechanism to promote their infection. By elucidating the molecular mechanism of temperature-dependent aquatic viral pathogenesis, our work may help to develop targeted prevention and control strategies against aquatic viral diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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