An aquatic virus exploits the IL6-STAT3-HSP90 signaling axis to promote viral entry

• Published in: PLoS pathogens 2023-04, Vol.19 (4), p.e1011320-e1011320
• Main 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
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Antibodies, Viral - metabolism; Aquaculture; Aquaculture industry; Biology and Life Sciences; Capsid protein; Capsid Proteins - metabolism; Carp; Carps; Development and progression; Disease; Diseases; Epidemics; Epidemiology; Fish Diseases; Fishes; Genetic aspects; Genomes; Growth; Health aspects; Heat shock proteins; Herpes viruses; Host-virus relationships; Hsp90 protein; Immune response; Infection; Infections; Interleukin-6 - metabolism; Molecular mechanics; Molecular modelling; Orthoreovirus; Pathogenesis; Plant virus diseases; Reoviridae; Reoviridae Infections - metabolism; Research and Analysis Methods; Seasonal variations; Seasonal variations (Diseases); Signaling; Stat3 protein; Temperature dependence; Vertebrates; Viral diseases; Viral infections; Viral proteins; Virus Internalization; Viruses; Water temperature
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1011320

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.