rig-i is required for the inhibition of measles virus by retinoids麻疹病毒的抑制需要rig - i类维生素a.pdfVIP

RIG-I Is Required for the Inhibition of Measles Virus by Retinoids 1,2. 1,2. 3 1 2 Kaitlin J. Soye , Claire Trottier , Chris D. Richardson , Brian J. Ward *, Wilson H. Miller Jr. * 1 McGill University Health Center Research Institute, Department of Infectious Diseases, McGill University, Montreal, Quebec, Canada, 2 Segal Cancer Centre, Lady Davis Institute for Medical Research, SMBD Jewish General Hospital, McGill University, Montreal, Quebec, Canada, 3 Department of Microbiology Immunology, Dalhousie University, Halifax, Nova Scotia Abstract Vitamin A can significantly decrease measles-associated morbidity and mortality. Vitamin A can inhibit the replication of measles virus (MeV) in vitro through an RARa- and type I interferon (IFN)-dependent mechanism. Retinoid-induced gene I (RIG-I) expression is induced by retinoids, activated by MeV RNA and is important for IFN signaling. We hypothesized that RIG-I is central to retinoid-mediated inhibition of MeV in vitro. We demonstrate that RIG-I expression is increased in cells treated with retinoids and infected with MeV. The central role of RIG-I in the retinoid-anti-MeV effect was demonstrated in the Huh-7/7.5 model; the latter cells having non-functional RIG-I. RAR-dependent retinoid signaling was required for the induction of RIG-I by retinoids and MeV. Retinoid signaling was also found to act in combination with IFN to induce high levels of RIG-I expression. RIG-I promoter activation required both retinoids and MeV, as indicated by markers of active chromatin. IRF-1 is known to be regulated by retinoids and MeV, but we found recruitment of IRF-1 to the RIG-I promoter by retinoids alone. Using luciferase expression constructs, we further demonstrated th