Porcine ANTXR1, Heparan Sulfate and Neu5Gc act as entry factors for Seneca Valley virus invasion

Abstract Seneca Valley virus (SVV) disease is a newly emerging infectious disease of pigs caused by SVV, which seriously endangers the pig industry. This study was set out to identify the essential host factors required for SVV entering porcine cells. Using a CRISPR/Cas9 library containing 93,859 sgRNAs that were designed to target approximately 22,707 porcine genes, we generated mutated porcine cell libraries, which were subjected to SVV challenge for enrichment of cells resistant to SVV infection. These resistant cells were subsequently analyzed to identify genes essential for SVV infection. We demonstrated that ANTXR1, a type I transmembrane protein encoded by ANTXR1 , heparan sulfate (HS), glycosaminoglycans modified by acetylation and sulfation of HS2ST1, and Neu5Gc, a non-human sialic acid catalyzed by CMAH, were the essential host factors for SVV entry into porcine cells. These results will be helpful to elucidate the pathogenesis of SVV and the development of prevention and control measures.