Febrile Temperature Acts through HSP70–Toll4 Signaling to Improve Shrimp Resistance to White Spot Syndrome Virus

In aquatic ectotherms, temperature plays a pivotal role in biological processes and the prevalence of viral diseases; however, the molecular mechanisms underlying these effects are not fully elucidated. In this study, we investigate the impact of elevated temperatures (32°C) on the immune response against white spot syndrome virus (WSSV) in shrimp (Litopenaeus vannamei). Our findings reveal that higher water temperatures, specifically 32°C, significantly inhibit WSSV replication and pathogenicity, thereby enhancing the survival rates of infected shrimp. Through transcriptome analysis and in vivo experiments, we identified heat shock protein 70 (HSP70) as a key factor in this thermal regulation of immunity. Shrimp maintained at 32°C, with silenced HSP70 expression, exhibited increased viral loads and reduced survival, underscoring the crucial protective role of HSP70 against WSSV at elevated temperatures. Our results further uncover the HSP70-Toll4-Dorsal-antimicrobial peptide (AMP) pathway as a key mediator of WSSV resistance at elevated temperatures. This pathway involves the interaction of HSP70 with the Toll4 receptor, resulting in the phosphorylation of Dorsal and the consequent modulation of expression of AMPs such as the anti-LPS factor (ALF) and lysozyme (LYZ) families. Taken together, these findings advance our understanding of temperature's role in disease dynamics in aquatic ectotherms, especially the unexpected roles of HSP70 in shrimp in facilitating the innate immune system's response to thermal stress, and suggest new approaches to managing WSSV in shrimp farming, such as environmental temperature control or HSP70 induction.