Cholesterol restriction primes antiviral innate immunity via SREBP1-driven noncanonical type I IFNs.

ABSTRACT: Cholesterol metabolism is associated with innate immune responses; however, the underlying mechanism remains unclear. Here, we perform chemical screening to isolate small molecules influencing RIG-I activity, a cytoplasmic viral RNA sensor. We find that statins, which inhibit cholesterol synthesis, dramatically enhance RIG-I-dependent antiviral responses in specific cell types. Since statins exhibit pleiotropic effects on type I interferon (IFN) responses, we further focus on their effects on RIG-I signaling. The restriction of cholesterol synthesis induces expression of noncanonical type I IFNs, such as IFN-ω, in an SREBP1 transcription factor-dependent manner. This pathway subsequently enhances RIG-I-mediated signaling following viral infection. Administration of statins augments RIG-I-d

SUBMITTER: Nishimura T 

PROVIDER: S-EPMC11772592 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature