Major capsid protein interacts with protein disulfide isomerase A3 to promote largemouth bass ranavirus adhesion and enhance viral infection.

Largemouth bass ranavirus (LMBV) is a DNA virus that threatens various aquatic animals, yet the mechanism by which it attaches to host cells to initiate infection remains poorly understood. Here, we report that the major capsid protein (MCP) of LMBV interacts with host protein disulfide-isomerase A3 (PDIA3). Subsequently, PDIA3 was also found to be localized on the host cell membrane, which may play a critical role in mediating virus adhesion and infection. Further investigation demonstrated that blocking the viral MCP protein with recombinant PDIA3 significantly reduced LMBV adhesion and infection. Similarly, adhesion and infection were markedly impaired when cell surface PDIA3 was blocked with specific antibodies. To further confirm the role of PDIA3 in LMBV adhesion, PDIA3 was expressed in human embryonic kidney 293T (HEK 293T) cells that were originally insensitive to LMBV. The results showed that PDIA3 expression in HEK 293T cells enhanced LMBV adhesion and infection. In addition, it was found that suppression of pdia3 expression could inhibit LMBV infection in largemouth bass. These results indicated that the interaction between MCP protein and PDIA3 plays a crucial role in promoting LMBV adhesion during virus entry and infection, deepening our understanding of the mechanism of LMBV infection and offering a potential target for controlling LMBV.