The Na ⁺ -K ⁺ -ATPase alpha subunit is an entry receptor for white spot syndrome virus

Cell surface receptors are crucial for mediating virus entry into host cells. Identification and characterization of virus receptors are fundamental yet challenging aspects of virology research. In this study, a BioID-based screening method was employed to identify the Na⁺-K⁺-ATPase alpha subunit (<i>Pv</i>ATP1A) as a potential receptor for white spot syndrome virus (WSSV) in the shrimp <i>Penaeus vannamei</i>. We demonstrated that <i>Pv</i>ATP1A interacted with the WSSV envelope protein VP28 via its multiple extracellular regions, thereby promoting viral internalization through caveolin-mediated endocytosis and macropinocytosis. Importantly, compared with previously identified WSSV receptors such as β-integrin, glucose transporter 1 (Glut1), and polymeric immunoglobulin receptor (pIgR), <i>Pv</i>ATP1A demonstrated significantly enhanced viral entry, indicating that <i>Pv</i>ATP1A is a crucial entry receptor of WSSV. This study not only presents a robust approach for screening virus receptors but also identifies <i>Pv</i>ATP1A as a promising target for the development of anti-WSSV therapeutics.