The Epstein-Barr virus (EBV) is highly penetrant in AIDS-associated non-Hodgkin's lymphomas where it is a key driver of the tumor phenotype. While EBV latency genes are critical for facilitating the tumor phenotype, the switch from latency to the lytic cycle is a critical aspect of a successful EBV infection program. As a result, the mechanisms driving this switch have been topics of active investigation over the years. Although EBV reactivation can be achieved in tissue culture through stimulation of the B-cell receptor (with anti-Ig) or the TGF-beta receptor (with ectopic TGF-beta), it is uncertain how common such events are in EBV-infected lymphocytes in vivo (work from David Thorley-Lawson's lab). The overarching hypothesis of this application is that EBV has evolved with a sensing mechanism for latently infected B-cells to detect when they encounter an epithelial cell environment. This model proposes that environmental cues from the oral/tonsil epithelium (in the late stages of the germinal center reaction, for example) trigger reactivation in B-cells, thereby facilitating the B-cell to epithelial cell viral transfer that is a fundamental first step n oral epithelial plaque formation and host- to-host transmission.

Public Health Relevance

The EBV infection cascade involves a complex series of events. A critical component of host-to-host transmission is the transfer of virus from B-cells harboring the latency viral reservoir to the oral epithelium where infectious virus is amplified an secreted into the saliva. We hypothesize that this transfer is orchestrated, in part, through cell o cell communication between epithelial cells and latently infected B-cells to increase the efficiency of this exchange pathway.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI101046-02
Application #
8458081
Study Section
Special Emphasis Panel (ZRG1-AARR-E (04))
Program Officer
Beisel, Christopher E
Project Start
2012-04-10
Project End
2017-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
2
Fiscal Year
2013
Total Cost
$353,675
Indirect Cost
$118,675
Name
Tulane University
Department
Pathology
Type
Schools of Medicine
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
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