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.