Epstein-Barr virus (EBV) is a B lymphotropic herpesvirus that usually persists benignly for the life time of the infected host, but can be predisposing for the development of certain lymphomas and carcinomas. Persistent infection in the peripheral blood of healthy carriers is quiescent, being restricted to latently infected, resting, memory B cells in which, at most, one or two latent genes are expressed. By comparison persistent infection in the mucosal lymphoid tissue appears to be more complex. There are infected naive and memory B cells, viral replication to produce infectious virus and at least one completely novel subset with a very high frequency of latently infected B cells. The virus is not randomly distributed through all of the B cells subsets. It is our hypothesis that the distribution of virus infected cells can be explained through analogy to normal B cell activation and differentiation within secondary lymphoid tissue. To test this idea we will focus on three main issues: 1. What is the nature of the novel B cell subset (CD38+CD10-IgD-) that we have found in the tonsils to be highly enriched for latently infected cells (approximately 1 in 500 are infected) and what is its relationship to classically defined memory B cells (CD38- CD10-IgD-) 2. Is EBV a mucosal specific virus i.e. is viral persistence actively maintained throughout the lymphoid tissue or quiescent everywhere except mucosal lymphoid tissue? Does the virus replicate in all lymphoid tissue or only mucosal lymphoid tissue? 3. Are virus infected cells in the lymphoid tissue able to undergo a germinal center reaction to enter the memory compartment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA065883-05
Application #
2850455
Study Section
Virology Study Section (VR)
Program Officer
Daschner, Phillip J
Project Start
1995-01-25
Project End
2004-01-31
Budget Start
1999-04-01
Budget End
2000-01-31
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Tufts University
Department
Pathology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111
Thorley-Lawson, David; Deitsch, Kirk W; Duca, Karen A et al. (2016) The Link between Plasmodium falciparum Malaria and Endemic Burkitt's Lymphoma-New Insight into a 50-Year-Old Enigma. PLoS Pathog 12:e1005331
Qiu, Jin; Smith, Pamela; Leahy, Leah et al. (2015) The Epstein-Barr virus encoded BART miRNAs potentiate tumor growth in vivo. PLoS Pathog 11:e1004561
Thorley-Lawson, David A (2015) EBV Persistence--Introducing the Virus. Curr Top Microbiol Immunol 390:151-209
Qiu, Jin; Thorley-Lawson, David A (2014) EBV microRNA BART 18-5p targets MAP3K2 to facilitate persistence in vivo by inhibiting viral replication in B cells. Proc Natl Acad Sci U S A 111:11157-62
Hawkins, Jared B; Delgado-Eckert, Edgar; Thorley-Lawson, David A et al. (2013) The cycle of EBV infection explains persistence, the sizes of the infected cell populations and which come under CTL regulation. PLoS Pathog 9:e1003685
Thorley-Lawson, David A; Hawkins, Jared B; Tracy, Sean I et al. (2013) The pathogenesis of Epstein-Barr virus persistent infection. Curr Opin Virol 3:227-32
Tracy, Sean I; Kakalacheva, Kristina; Lunemann, Jan D et al. (2012) Persistence of Epstein-Barr virus in self-reactive memory B cells. J Virol 86:12330-40
Smith, Pamela A; Merritt, David; Barr, Leah et al. (2011) An orthotopic model of metastatic nasopharyngeal carcinoma and its application in elucidating a therapeutic target that inhibits metastasis. Genes Cancer 2:1023-33
Hawkins, Jared B; Jones, Mark T; Plassmann, Paul E et al. (2011) Chemotaxis in densely populated tissue determines germinal center anatomy and cell motility: a new paradigm for the development of complex tissues. PLoS One 6:e27650
Qiu, Jin; Cosmopoulos, Katherine; Pegtel, Michiel et al. (2011) A novel persistence associated EBV miRNA expression profile is disrupted in neoplasia. PLoS Pathog 7:e1002193

Showing the most recent 10 out of 47 publications