Influenza virus infection reprograms cholesterol biosynthesis to facilitate virus replication by the TAK1-RORγ axis.

ABSTRACT: Infection and replication of enveloped viruses require host cells to supply substantial amounts of cellular cholesterol for processes such as binding, entry, trafficking, assembly, and budding. However, the mechanisms by which influenza A virus (IAV) regulates cholesterol biosynthesis remain poorly understood. In this study, we demonstrate that IAV infection induces the expression of the retinoic acid-related orphan receptor γ (RORγ), an orphan nuclear receptor, which cooperates with the sterol regulatory element-binding protein-2 (SREBP2) to regulate the expression of the 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase (HMGCR), a key enzyme in cholesterol biosynthesis. RORγ knockout and treatment with two RORγ inhibitors, XY018 and GSK805, suppress IAV-induced HMGCR expression,

SUBMITTER: Zhang J 

PROVIDER: S-EPMC12574845 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature