Research in the Krishnamurthy lab focuses on host response during viral infections. Our studies address the fundamental mechanisms by which cells resist infection and how cells know they are infected by a virus. The innate immune pathway is the first line of defense against viruses and functions to limit viral replication and spread. Diverse signaling pathways are activated in host cells in response to virus infections and understanding these interactions at the molecular and cellular level will identify novel host factors to develop broad antiviral therapies against different types of viruses. Our research aims to define the role of 1) RNA signaling pathways and 2) Integrated Stress Response pathways in determining the outcome of viral infections.
Double-stranded RNAs produced during viral infections serve as pathogen associated molecular patterns (PAMPs) to stimulate interferon (IFN) production. Subsequent activation of an IFN-regulated endoribonuclease, Ribonuclease L, produces immunostimulatory RNAs from cellular and viral RNAs that participate in signaling pathways to 1) produce IFN and proinflammatory cytokines, 2) induce autophagy and programmed cell death and 3) activate stress response pathways. Our studies use gene-targeting, biochemical, molecular and cell biological techniques as well as RNA and proteomic based approaches to unravel the complex nature of host-viral interactions in human, murine and fish cells.
Research projects:
Activation of stress response during viral infection
Regulation of autophagy and cell death pathways
RNA helicases and dsRNA-binding proteins in innate immunity
Altering cytoskeletal dynamics and innate immune response
Immune evasion in Aquatic Rhabdoviral Pathogens
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