The class B scavenger receptor 2 act as a proviral factor in largemouth bass ranavirus infection

Largemouth bass ranavirus (LMBRaV) is a serious epidemic pathogen of Largemouth bass (Micropterus salmoides) and cause severe economic losses to aquaculture. As a key receptor in innate immune responses, the function of scavenger receptor class B member 2 (SRB2) during virus infection has not been reported in fish to date. This study found that M. salmoides SRB2 (MsSRB2) is a relatively conserved sequence with two transmembrane domains and shares 65.41%-98% sequence identities with SRB2 from other vertebrates. Quantitative real-time PCR (qRT-PCR) results showed that MsSRB2 is predominantly expressed in the heart, with the lowest expression level in the spleen. Following LMBRaV infection, the MsSRB2 mRNA levels in the spleen, kidney, and liver of infected fish first increased and then decreased. After over-expressed in Epithelioma Papulosum Cyprini (EPC), MsSRB2 was mainly located on the late endosome, and can co-loalized with the major capsid protein (MCP) of LMBRaV (LMBRaV MCP). Additionally, MsSRB2 over-expression significantly inhibited LMBRaV replication in EPC cells. In contrast, knockdown of MsSRB2 in M. salmoides led to a marked increase in survival rate and a significant reduction in virus load in the spleen and liver. Based on these distinct outcomes from invitro and invivo assays, we hypothesize that MsSRB2 is hijacked by LMBRaV as a potential intracellular receptor in the presence of relevant host components, which facilitates immune evasion and ultimately enhances viral replication. This study provides new insights into understanding virus-host interactions in teleosts and lays a theoretical foundation for the development of novel prevention and control strategies against ranavirus disease.