Cholesterol 25-Hydroxylase inhibits bovine parainfluenza virus type 3 replication through enzyme activity-dependent and -independent ways

Bovine parainfluenza virus type 3 (BPIV3) is one of the most important pathogens associated with bovine respiratory diseases in both young and adult cattle widespreadly around the world. The host factors which participate in the Infection of BPIV3 are poorly understood. Here, we found the bovine protein Cholesterol 25-hydroxylase (CH25 H) plays an important role in the Infection of BPIV3. CH25H is a multi-transmembrane and endoplasmic reticulum-related Enzyme that catalyzes oxidation reaction of Cholesterol to production of 25-hydroxycholesterol (25HC) and significantly inhibits the replication of several viruses. In this study, we found that CH25H is an interferon-stimulated gene (ISG), which taken part in the Antiviral innate immunity. In addition, the overexpression of CH25H could inhibit the replication of BPIV3, and 25HC significantly inhibited BPIV3 Infection by preventing the synthesis of both virus antigenomic RNA (cRNA) and genomic RNA (gRNA) in MDBK cells. Interestingly, CH25H-M, a mutant lacking hydroxylase activity, still had an Antiviral effect against BPIV3. Taken together, our findings highlight the Antiviral function of CH25H during BPIV3 Infection, and suggest that CH25H inhibits viral Infection through both Enzyme activity-dependent and -independent ways.