Grant: Operating Grant

The innate immune system is the first line of host defense for organisms that possess an adaptive immune system. It allows discrimination between self and non-self, restricts pathogens dissemination, eliminates pathogens and instructs pathogen-specific adaptive immune response. In order to establish infection, viruses need to either suppress or escape from host immune defense systems. An effective way to treat viral infection is to restore immunity upon virus evasion strategies by modulating the host innate immune response. In a genome-wide lentiviral-based RNA interference (RNAi) screen designed to silence expression of the 16,000 human genes, one at a time, in cells subsequently infected with Sendai Virus (SeV), we identified 235 candidate genes that regulate the virus-mediated early antiviral immune response. This study represents a first step to the extensive understanding of pathogen recognition molecule-mediated antiviral signaling pathways, and paves the way to the development of immunomodulatory pan-therapies for a broad spectrum of viral infections. By elucidating the mechanism of action of new regulators of the innate antiviral immunity and validating the modulatory role of candidate genes for selected RNA viruses, a chemical high throughput screening approach will be used to validate novel antiviral pan-targets. The ultimate goal is to identify lead therapeutic molecules for established and emergent RNA diseases such as hepatitis C virus (HCV), human immunodeficiency virus 1 (HIV-1) and may come to include Avian influenza (FLU) H5N1 virus infection.