Postdoctoral Associate

Structural Biology

Stanford University School of Medicine (Stanford, CA)

Joseph D. Puglisi

RNA viruses sensing mechanism by innate immune receptor RIG-I

The innate immune system is a first line of defense against pathogen infection. The response to pathogens by the innate immune system of mammals is initiated by the detection of pathogen components by host pattern recognition receptors. These receptors specifically recognize molecules such as virual RNA and DNA, pathogen cell wall components, or flagellar proteins. Viral RNA is recognized in the endosome by membrane-bound Toll-like receptors, or in the cytoplasm by retinoic acid inducible gene 1(RIG-I, also known as DDX58) and melanoma differentiation associated antigen 5 (MDA5, also known as IFIH1 or Helicard). Upon recognition of cytosolic viral RNA, RIG-I and MDA5 bind to the adaptor protein IPS-1, which is located in the outer mitochondrial membrane. The interactions of RIG-I or MDA5 with IPS-1 initiate downstream sinaling to interferon regulator 3(IRF-3), IRF7 and NF-kappaB transcription factors, resulting in the antiviral response by interferon production and activation of interferon-stimulated genes as well as NF-kappaB target genes. Our research interests focus on RNA sensing mechanism by RIG-I. We are working on address how viruses RNA bind to RIG-I by its second structures. The main tools we prefer to use are NMR methods.