Virus infections, such as influenza A epidemic, Ebola hemorrhagic fever, Middle East respiratory syndrom, Zika virus infection are important diseases and outbreaks of newly emerging viruses are serious problems for modern society. Higher animals, including humans, are genetically equipped with mechanisms, collectively known as innate immunity, to counteract viral infections. During the course of replication, many viruses generate double-stranded (ds)RNA, which is virtually absent in normal cells and likely serves as a “foreign molecule” in cells. An RNA helicase, RIG-I, functions as a sensor for viral dsRNA. RIG-I is composed of three domains : a Caspase recruitment domain (CARD), a DExD/H helicase domain, and a C-terminal domain (CTD)(Figure). CTD senses viral dsRNA produced in the cytoplasm, leading to a conformational change. This conformational change releases CARD, which signals to downstream, resulting in the activation of genes including those for type I interferon and other cytokines. The purpose of our project is to clarify the molecular mechanism underlying the antiviral innate immunity regulated by RIG-I, and to develop new diagnostic and therapeutic means for viral infections.
Laboratory of Molecular and Cellular Immunology Keyword
virus interferon innate immunity RNA helicase double-strand RNA cytokine influenza immunology RNA hepatitis B virus