Thermal stress enhances AnHV-1 replication in chicken embryonic fibroblasts and embryos by HSP90B1 induction and metabolic alterations.

Anatid alphaherpesvirus 1 (AnHV-1) is an emerging threat that induces severe disease and death in both domestic and wild waterfowl. Birds have an elevated basal body temperature, and suffer at times from environmental heat stress, yet little are known about the mechanisms involved in avian virus replication at higher temperatures. In this study, we examined the effects of hyperthermia on replication dynamics and host cellular responses to AnHV-1 in chicken embryonic fibroblast cultures and an in ovo model. Hyperthermic conditions dramatically increased AnHV-1 replication, viral gene expression and protein accumulation in vitro and in ovo. Elevated temperature was associated with coordinated changes in metabolic and mitochondrial parameters indicative of elevated glucose uptake, modulated expression of key glycolytic enzymes, elevated ATP production, and altered intracellular NADPH levels consistent with increased redox demand. Hyperthermia was associated with increased mitochondrial membrane potential, ATP production and reactive oxygen species generation while reducing the expression of selected antiviral immune-response genes. These changes were suggestive that thermal stress remodels intracellular environment to promote viral replication. Pharmacological inhibition of these pathways reduced viral replication, supporting their potential contribution to enhanced AnHV-1 replication under elevated temperature.