Medical Research

University of California, Davis

Ben Montpetit, Priva Shah, Christopher Fraser, Richard Wozniak
Davis, CA
$1,000,000
June 2018

Zika, Hepatitis C, Dengue, and West Nile of the Flaviviridae virus family infect hundreds of millions of people, causing widespread morbidity and mortality.  A prominent example is the recently discovered congenital Zika syndrome characterized by severe microcephaly and other developmental defects.  Except for Hepatitis C, there are no approved anti-viral treatments for these viruses, despite decades of research.  A central tenet of Flaviviridae biology, and one that defines therapeutic strategies, is that virus replication occurs within the cytoplasm of host cells.  Investigators from the University of California, Davis and the University of Alberta in Canada are challenging this dogma by showing, using highly sensitive and specific detection techniques, that the RNA genomes (vRNAs) of Zika and Hepatitis C enter and leave the host cell nucleus during the course of an infection.  This breakthrough requires a paradigm shift away from a cytoplasm centric view of Flaviviridae biology and a re-evaluation of how researchers study and combat these viruses.  However, before the team can leverage this knowledge for societal benefit (e.g. therapeutics), they must understand, at a molecular and mechanistic level, why these viral RNAs travel through the nucleus and engage nuclear processes, and how this benefits the virus.  They will tackle these questions using highly innovative approaches that will allow them to construct dynamic and cell specific systems-level interaction networks between vRNAs and host cell nuclear factors.  The investigators expect these high-risk, high-reward endeavors will produce new paradigms and foster novel pan-Flaviviridae therapeutic opportunities.

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