Hypoxia inducible factor-1α facilitates transmissible gastroenteritis virus replication by inhibiting type I and type III interferon production

Transmissible gastroenteritis virus (TGEV) is characterized by watery diarrhea, vomiting, and dehydration and is associated with high mortality especially in newborn piglets, causing significant economic losses to the global pig industry. Hypoxia inducible factor-1 alpha (HIF-1 alpha) has been identified as a key regulator of TGEV-induced inflammation, but understanding of the effect of HIF-1 alpha on TGEV infection remains limited. This study found that TGEV infection was associated with a marked increase in HIF-1 alpha expression in ST cells and an intestinal organoid epithelial monolayer. Furthermore, HIF-1 alpha was shown to facilitate TGEV infection by targeting viral replication, which was achieved by restraining type I and type III interferon (IFN) production. In vivo experiments in piglets demonstrated that the HIF-1 alpha inhibitor BAY87-2243 significantly reduced HIF-1 alpha expression and inhibited TGEV replication and pathogenesis by activating IFN production. In summary, we unveiled that HIF-1 alpha facilitates TGEV replication by restraining type I and type III IFN production in vitro, ex vivo, and in vivo. The findings from this study suggest that HIF-1 alpha could be a novel antiviral target and candidate drug against TGEV infection.