Neonatal Fc receptor is a functional receptor for human astrovirus

Abstract

SummaryHuman astrovirus (HAstV) is a global cause of gastroenteritis in infants, the elderly, and immunocompromised people. However, its infection mechanism is not fully understood, with its functional receptor not yet discovered. Here, we identify neonatal Fc receptor (FcRn) as a functional receptor for HAstV (mamastrovirus 1) using genome-wide CRISPR-Cas9 library screening in Caco2 cells. Deletion ofFCGRTorB2M, which encode subunits of FcRn, rendered Caco2 cells and intestinal organoid cells unsusceptible to HAstV. We also show that human FcRn expression renders non-permissive MDCK cells susceptible and that FcRn directly binds HAstV spike protein. Thus, our findings provide insight into the entry mechanism of HAstV.