biostudies-literatureJiang LNational Natural Science Foundation of Chinae0117522https://www.ebi.ac.uk/biostudies/studies/S-EPMC9555151biostudies-literatureUnknown96(19)The frequent outbreak of grass carp hemorrhagic disease caused by grass carp reovirus (GCRV), especially the mainly prevalent type II GCRV (GCRV-II), has seriously affected the grass carp culture in China. However, its pathogenic mechanism is still far from clear. In this study, the GCRV-II outer capsid protein VP35 was used as bait to capture interacting partners from <i>Ctenopharyngon idellus</i> kidney (CIK) cells, and heat shock protein 90 (Hsp90) was selected and confirmed interacting with VP35 through the C-terminal domain of Hsp90. Knockdown of Hsp90 or inhibition of Hsp90 activity suppressed GCRV-II proliferation, demonstrating that Hsp90 is an essential factor for GCRV-II proliferation. The confocal microscopy and flow cytometry showed that Hsp90 localized at both membrane and cytJournal of virologyHsp90 Regulates GCRV-II Proliferation by Interacting with VP35 as Its Receptor and Chaperone.PMC955515131972832317250263217301431930114Jiang LLiu AQZhang YAZhang CTu JfalseHsp90 Regulates GCRV-II Proliferation by Interacting with VP35 as Its Receptor and Chaperone.The frequent outbreak of grass carp hemorrhagic disease caused by grass carp reovirus (GCRV), especially the mainly prevalent type II GCRV (GCRV-II), has seriously affected the grass carp culture in China. However, its pathogenic mechanism is still far from clear. In this study, the GCRV-II outer capsid protein VP35 was used as bait to capture interacting partners from <i>Ctenopharyngon idellus</i> kidney (CIK) cells, and heat shock protein 90 (Hsp90) was selected and confirmed interacting with VP35 through the C-terminal domain of Hsp90. Knockdown of Hsp90 or inhibition of Hsp90 activity suppressed GCRV-II proliferation, demonstrating that Hsp90 is an essential factor for GCRV-II proliferation. The confocal microscopy and flow cytometry showed that Hsp90 localized at both membrane and cyt2022-01-01T00:00:00Z2022 Oct2026-06-14T07:50:41.548Z2025-02-18T23:35:20.93ZS-EPMC95551513610264710.1128/jvi.01175-22