Digital Data

PRRSV continues to cause severe financial losses to global swine industry. It is feasible to develop safe and effective antiviral strategies based on the initial step of viral infection, that is the recognition of the virus by the cellular entry factors. However, the interactions between PRRSV and host factors initiating viral attachment and internalization are not fully understood yet. In this study, ATP1A1 was identified to promote both PRRSV-2 attachment and internalization through macropinocytosis and caveolae/raft-dependent endocytosis. These findings reveal an unrecognized entry mechanism of PRRSV-2 and provide novel insights for the development of antiviral drugs and vaccines against the virus.