Dissertation Defense Announcement
To:  The George Mason University Community

Candidate: Todd M. Bell
Program: PhD in Biosciences
 
Date:   Tuesday May 23, 2017
Time:   10:00 AM
Place:  George Mason University
 Science & Tech campus
  IABR, Room 1004 
 
Title: "Tinkering with Translation to Handcuff Rift Valley Fever Virus"

Committee Chair: Dr. Kylene Kehn-Hall
Committee Members:  Dr. Lance Liotta, Dr. Virginia Espina, Dr. Amanda Fales-Williams

All are invited to attend the defense.

ABSTRACT:
Despite over 60 years of research on antiviral drugs, very few are FDA approved to treat acute viral infections. Rift Valley fever virus (RVFV), an arthropod borne virus that causes hemorrhagic fever in severe cases, currently lacks effective treatments. Existing as obligate intracellular parasites, viruses have evolved to manipulate host cell signaling pathways to meet their replication needs. Specifically, translation modulation is often necessary for viruses to establish infection in their host. Here we demonstrated phosphorylation of p70 S6 kinase, S6 ribosomal protein, and eIF4G following RVFV infection in vitro through western blot analysis and in a mouse model of infection through reverse phase protein microarrays (RPPA). Inhibition of p70 S6 kinase through rapamycin treatment reduced viral titers in vitro and increased survival and mitigated clinical disease in RVFV challenged mice. Additionally, the phosphorylation of p70 S6 kinase was decreased following rapamycin treatment in vivo. Collectively these data demonstrate modulating p70 S6 kinase can be an effective antiviral strategy.  We also examined another translation kinase, p90RSK, and found inhibition of this kinase resulted in increased viral replication.  This increase in viral replication in the face of p90RSK inhibitory drugs suggests activation of this enzyme is an antiviral event, thus further elucidating how various translation kinases are involved in infection.

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