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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-AARR-E (04))
Program Officer
Beisel, Christopher E
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Tulane University
Schools of Medicine
New Orleans
United States
Zip Code
Striker, Rob; Mehle, Andrew (2014) Inhibitors of peptidyl proline isomerases as antivirals in hepatitis C and other viruses. PLoS Pathog 10:e1004428
Martin, Elizabeth C; Krebs, Adrienne E; Burks, Hope E et al. (2014) miR-155 induced transcriptome changes in the MCF-7 breast cancer cell line leads to enhanced mitogen activated protein kinase signaling. Genes Cancer 5:353-64
Zhang, Wensheng; Edwards, Andrea; Flemington, Erik et al. (2014) Somatic mutations favorable to patient survival are predominant in ovarian carcinomas. PLoS One 9:e112561
Martin, Elizabeth C; Rhodes, Lyndsay V; Elliott, Steven et al. (2014) microRNA regulation of mammalian target of rapamycin expression and activity controls estrogen receptor function and RAD001 sensitivity. Mol Cancer 13:229
Xu, Guorong; Strong, Michael J; Lacey, Michelle R et al. (2014) RNA CoMPASS: a dual approach for pathogen and host transcriptome analysis of RNA-seq datasets. PLoS One 9:e89445
Qin, Zhiqiang; Dai, Lu; Trillo-Tinoco, Jimena et al. (2014) Targeting sphingosine kinase induces apoptosis and tumor regression for KSHV-associated primary effusion lymphoma. Mol Cancer Ther 13:154-64
Strong, Michael J; Lin, Zhen; Flemington, Erik K (2014) Expanding the conversation on high-throughput virome sequencing standards to include consideration of microbial contamination sources. MBio 5:e01989
Strong, Michael J; Xu, Guorong; Morici, Lisa et al. (2014) Microbial contamination in next generation sequencing: implications for sequence-based analysis of clinical samples. PLoS Pathog 10:e1004437
O'Grady, Tina; Cao, Subing; Strong, Michael J et al. (2014) Global bidirectional transcription of the Epstein-Barr virus genome during reactivation. J Virol 88:1604-16
Martin, Elizabeth C; Elliott, Steven; Rhodes, Lyndsay V et al. (2014) Preferential star strand biogenesis of pre-miR-24-2 targets PKC-alpha and suppresses cell survival in MCF-7 breast cancer cells. Mol Carcinog 53:38-48

Showing the most recent 10 out of 12 publications