Class B scavenger receptor resists WSSV replication by recognizing the viral lipid molecule and promoting phagocytosis

Class B scavenger receptors (SRBs) have been well-studied in bacteria-induced immune responses in invertebrates. However, the status of SRB-defending viruses remains unclear. In this study, we identified a scavenger receptor in <i>Procambarus clarkii</i> (crayfish), which is homologous to mammalian SRBs, and designated it as <i>Pc</i>SRB. The expression of <i>Pc</i>SRB was upregulated after the WSSV challenge. The survival rate of crayfish was decreased, but the WSSV copy number increased after <i>Pc</i>SRB knockdown during virus invasion. In addition, <i>Pc</i>SRB bound to WSSV. Furthermore, we detected how <i>Pc</i>SRB interacted with WSSV, and we found that <i>Pc</i>SRB could bind to cholesta-3,5-diene, (CD3,5), a novel WSSV lipid ligand, rather than dibutyl phthalate (DBP). Besides, <i>Pc</i>SRB could bind to VP19, VP26, and VP28, rather than VP24. Mutant-binding experiments demonstrated that the hydrophobic domain (130-180 aa) of <i>Pc</i>SRB is important for recognizing WSSV. Furthermore, <i>Pc</i>SRB might promote lysosomal eliminating function to degrade WSSV. Altogether, we identified a new mechanism for scavenger receptor recognition and resistance to WSSV.IMPORTANCE<i>Pc</i>SRB could bind to WSSV directly. <i>Pc</i>SRB could interact with WSSV via binding to lipid molecule CD3,5 and viral envelope proteins. <i>Pc</i>SRB could influence lysosomal activation.