Transferrin receptor 1 (TfR1) functions as an entry receptor for scale drop disease virus to invade the host cell via clathrin-mediated endocytosis

Abstract

TfR1, a dimeric glycoprotein classified as a type II transmembrane receptor, facilitates the cellular internalization of holo-transferrin. In several mammalian and avian RNA viruses and small DNA viruses, TfR1 serves as a crucial receptor to mediate the entry of viruses into host cells. As an emerging large DNA virus, SDDV poses an emerging threat to teleosts globally; however, its underlying pathogenic mechanisms remain poorly understood. In this study, we are the first to identify mf TfR1 as a crucial receptor for SDDV entry. We demonstrated a specific interaction between mf TfR1 and the major capsid protein (MCP) of SDDV, with the helical domain of mf TfR1 acting as the binding site. Moreover, we confirmed that SDDV enters cells through mf TfR1-mediated clathrin-dependent endocytosis. This work highlights the essential role of TfR1 in aquatic DNA viral infections and establishes the theoretical foundation for developing targeted therapeutic strategies against SDDV.