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- Title
An aquatic virus exploits the IL6-STAT3-HSP90 signaling axis to promote viral entry.
- Authors
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; Li, Junhua
- 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.
- Subjects
HEAT shock proteins; CYTOSKELETAL proteins; VIRAL proteins; CTENOPHARYNGODON idella; IRIDOVIRUSES; VIRUS diseases; HERPESVIRUSES; ARTIFICIAL membranes
- Publication
PLoS Pathogens, 2023, Vol 18, Issue 4, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1011320