Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
ISSN: 2155-9899
Rongtuan Lin1,2, Yiliu Liu1,2, Sidi Mehdi Belgnaoui1, Alexander Sze1,2, Marie-Line Goulet1 and Chunfu Zheng3
1Lady Davis Institute, Canada 2McGill University, Canada 3Soochow University, China
Posters-Accepted Abstracts: J Clin Cell Immunol
The innate immune response to virus infection plays a critical role in limiting virus multiplication and pathogenesis. Central to the innate antiviral response is the rapid induction of type I interferon (IFN) expression; IFN gene expression is tightly regulated by the recognition of extra- and intra-cellular signals, generated during primary infection. The viral genome or viral replicative intermediates containing 5ΓΆΒ?Β?triphosphate (5ΓΆΒ?Β?ppp) RNA binds to RIG-I and ultimately leads to the production of proinflammatory cytokines and anti-viral factors, as well as type I interferons (IFNs) that amplifies the antiviral immune response. Given that viral RNA-RIG-I interaction is the initial trigger of the innate and adaptive immune response, an attractive strategy for the development of an efficient and broad spectrum antiviral therapy to inhibit virus infection, involves the use of RIG-I agonist that mimic viral RNA to activate the host defense. Our previous study demonstrated that treatment of various cell lines and primary cells with 5ΓΆΒ?Β?ppp RNA in vitro led to protection against infection and replication of a broad range of RNA and DNA viruses. In vivo, intravenous administration of 5ΓΆΒ?Β?ppp RNA protected mice from a challenge with H1N1 and H5N1 Influenza virus. Our recent study shown that 5ΓΆΒ?Β?ppp RNA has the ability to counteract Ebola virus infectivity in vitro. We identified STING among a plethora of differentially expressed genes induced by the RIG-I agonist 5ΓΆΒ?Β?ppp RNA. STING has been identified as an RIG-I signaling cofactor and a critical adaptor protein required for cytosolic DNA and cyclic dinucleotides (CDNs) triggered immune responses. We further detail the mechanism of STING regulation. Furthermore, our results also unveiled an essential contribution of STING in the establishment of the 5ΓΆΒ?Β?ppp RNA induced antiviral responses during HSV1 infection.Taken together, these observations demonstrate that the STING is induced via RIG-I signaling and up-regulated STING is essential for 5ΓΆΒ?Β?ppp RNA mediated HSV restriction.
Email: rongtuan.lin@mcgill.ca