Genome-wide CRISPR/Cas9 knockout screen identifies host factors essential for bovine parainfluenza virus type 3 replication

Bovine parainfluenza virus type 3 (BPIV3) is a leading cause of respiratory illness in cattle and a primary component of the bovine respiratory disease complex (BRDC), resulting in significant economic losses. Understanding the mechanisms of BPIV3 infection, particularly the entry process, is essential for developing effective control measures. Identifying specific host factors that viruses exploit during their life cycle can reveal critical vulnerabilities for potential antiviral targets. We established a genome-wide CRISPR/Cas9 knockout screen in bovine cells to identify host factors involved in viral infections. Our screen identified several key host factors required for BPIV3 infection, including the sialic acid transporter SLC35A1 and the Sm-like protein LSM12. Further mechanistic analysis revealed that these factors played critical roles at distinct stages of the BPIV3 entry process. These findings not only advance our understanding of how BPIV3 infects host cells but also identify potential host targets for inhibiting infection and developing novel antiviral strategies.