July 2011


Options: Use Monospaced Font
Show Text Part by Default
Show All Mail Headers

Message: [<< First] [< Prev] [Next >] [Last >>]
Topic: [<< First] [< Prev] [Next >] [Last >>]
Author: [<< First] [< Prev] [Next >] [Last >>]

Print Reply
Diane StGermain <[log in to unmask]>
Reply To:
Diane StGermain <[log in to unmask]>
Mon, 25 Jul 2011 14:58:19 -0400
text/plain (73 lines)
> Reminder: Thesis Defense Announcement
> To: The George Mason University Community
> *Candidate: Alan Baer
> Program: Master of Science in Biology
> *
> *Date: Tuesday July 26, 2011
> Time: 10:00 a.m.
> Place: George Mason University, Prince William campus
> <>
> Bull Run Hall, Room 246
> *Thesis Chair: Dr. Kylene Kehn-Hall
> Title: " Induction of DNA Damage Signaling Cascade Upon Rift
> Valley Fever Virus (RVFV) Infection"***
> *
> A copy of the thesis is on reserve in the Johnson Center Library,
> Fairfax campus. The thesis will not be read at the meeting, but
> should
> be read in advance. All members of the George Mason University
> community
> are invited to attend.
> Rift Valley fever virus (RVFV), family Bunyaviridae, is a highly
> pathogenic arthropod-borne virus infecting a wide range of
> vertebrate
> hosts. Of particular interest is the replication dispensable NSs
> protein, a major virulence factor, which unique among cytoplasmic
> replicating bunyaviruses forms large filamentous fibril bundles in
> the
> nucleus. Past studies have shown NSs to be a multifaceted
> protein,
> inducing the post-transcriptional down regulation of dsRNA-
> dependent
> protein kinase (PKR), preventing phosphorylation of eIF2alpha and
> promoting viral translation in infected cells, as well as acting
> as a
> general inhibitor of IFN and cellular transcription. Our previous
> studies indicated that p53 was phosphorylated at Ser15 and Ser46
> as well
> as demonstrating an increase in cellular levels of the antioxidant
> enzyme, superoxide dismutase 1 (SOD1), following infection with
> P53 phosphorylation is important for many cellular process
> including
> apoptosis and DNA damage signaling. As DNA damage sensors play
> central
> roles in the cellular response to genotoxic stress and viral
> manipulation has been well characterized in other systems, we
> hypothesized that these pathways might be involved in RVFV
> pathogenicity
> and indeed found an NSs dependant induced phosphorylation at
> specific
> DNA damage signaling checkpoints following RVFV infection: p-ATM
> (Ser1981), p-Chk.2 (Thr68), p-H2A.X (Ser139)* *and p-P53 (Ser15),
> as
> well as concurrent S phase arrest. Use of specific checkpoint
> inhibitors ATM and Chk.2 resulted in a marked decrease in S phase
> arrest
> as well viral production. By identifying these cellular viral
> targets
> we hope to develop therapeutics targeted to the host, establishing
> a
> much broader range of targets with a decreased likelihood of viral
> adaptation.
> ###