Investigating the Mechanism of NLRP1 Inflammasome Activation by Dengue Virus Protease
Dengue virus (DENV) is the leading cause of death in dengue-endemic areas. An infection resulting from DENV can manifest as serious human disease, such as Dengue hemorrhagic fever or Dengue shock syndrome. Currently there is no effective vaccine to prevent the infection. My project seeks to understand critical host-virus interactions between DENV and multi-protein innate immune cytosolic complexes called inflammasomes, which initiate downstream proinflammatory signaling. Inflammasomes are typically thought to detect pathogen-encoded ligands. In contrast, NLRP1the focus of this proposaldetects protease activity. I will be focusing on the molecular determinants of human NLRP1 sensing of the DENV NS2B3 protease, and how this recognition event leads to inflammasome activation. A full understanding of the molecular events leading to DENV-mediated activation of the NLRP1 inflammasome is crucial to developing improved mouse models to study host immunity and pathogenesis in the setting of in vivo DENV infection.
Message to Sponsor
- Major: MCB-Infectious Diseases
- Sponsor: Pergo Fund
- Mentor: Russell Vance