Pvf/Pvr signaling relieves white spot syndrome virus-induced lipid consumption to inhibit viral infection in shrimp

Platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF)-related factors (Pvfs) are highly conserved and widespread growth factors whose signaling is mediated by the PDGF/VEGF-related receptor (Pvr). Pvf/Pvr signaling is involved in the regulation of development, immunity, and metabolism of organisms and can be a key therapeutic target for a variety of clinical diseases. However, the functions and mechanisms of Pvf/Pvr signaling in viral infections are largely unknown. In the present study, we found that Pvf/Pvr family members, MjPvf2/MjPvr3, inhibit white spot syndrome virus (WSSV) Infection by regulating lipid metabolism in the kuruma shrimp (Marsupenaeus japonicus). WSSV Infection caused a pronounced reduction in triglyceride content, whereas the activation of MjPvf2/MjPvr3 signaling relieved lipid consumption and suppressed viral Infection. Mechanistically, WSSV Infection enhanced MjPvf2/MjPvr3 signaling, leading to the activation of extracellular signal-regulated kinase (ERK) and sterol regulatory element-binding protein (SREBP), and subsequent induction of hydroxysteroid dehydrogenase (MjHSD) expression. MjHSD promoted lipid synthesis and restored lipid levels, thereby restricting viral replication. Importantly, pharmacological inhibition of lipid synthesis eliminated the Antiviral effect of MjPvf2/MjPvr3 signaling. In conclusion, this study revealed the significance and mechanism of Pvf/Pvr signaling in Antiviral immunity, providing novel insights into WSSV prevention and control in shrimp aquaculture.

Importance: Viral Infection affects host lipid metabolism. This process depletes the host's lipids to support viral replication. Pvf/Pvr signaling is widely involved in host physiological processes, but its role in viral Infection has not been clarified. We demonstrate that Pvf/Pvr signaling exerts an Antiviral effect by relieving the lipid consumption caused by white spot syndrome virus (WSSV) Infection in shrimp. This study provides new insights into the effects of Pvf/Pvr signaling on Antiviral immunity and highlights the complexity of lipid metabolism under WSSV Infection.