Virology and Microbiology

Emerging or re-emerging virological threat represents a major public health problem. Pathogenic virus infection is controlled in large part by the host antiviral immune response. 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 5’triphosphate (5’ppp) RNA binds to RIG-I and ultimately leads to the production of pro-inflammatory 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 replication involves the use of RIG-I agonist that mimic viral RNA to activate the host defense. Our recent work demonstrated that the RIG-I agonist molecules we have designed in-house have potent antiviral activity against a range of RNA and DNA viruses in-vitro and confer protection against Influenza H1N1 and HSV-1 virus infection in-vivo in the murine model. Our ongoing study demonstrated that RIG-I agonist also has potent antiviral activity against Ebola viruses in-vitro and in-vivo in the murine model. We seek to investigate the potential of 5’pppRNA as a prophylactic and therapeutic antiviral agent against Ebola virus and the mechanisms responsible for the observed protective effect.