EBV Conference 2008 Guangzhou - Baylor College of Medicine

43 (RegID: 1760; 1761; 1763)
Shidong Ma
Institution: McArdle Laboratory for Cancer Research, University of WIsconsin-Madison
e-mail: mashidong@oncology.wisc.edu
CO-TRANSPLANTED HUMAN THYMUS IMPROVES CONTROL OF EPSTEIN-BARR VIRUS
INFECTION IN A HUMANIZED-SCID-GAMMA C-/- MOUSE MODEL, AND LYTIC VIRAL
INFECTION INCREASES LYMPHOMA NUMBER.
Shidong Ma, Deepika Rajesh, Ruth Sullivan, William J. Burlingham, Xiaoping Sun, Margaret L. Gulley,
and Shannon C. Kenney
Oralabstract:
NOD/SCID/gamma C-/- mice injected with human CD34+ hematopoitic stem cells provide a model for
studying EBV pathogenesis in the context of a human immune system. Whether transplanted human
thymic tissue improves control of EBV infection, and whether lytic EBV infection increases lymphomas,
in this model remains unclear. We compared the effects wild-type EBV infection, versus infection with a
lytic-defective mutant (BZLF1-deleted) in mice injected with human fetal CD34+ cells in the presence or
absence human thymus tissue. Mice were injected intraperitoneally with 2700 infectious units of wt or
lytic-defective B95-8 virus. In the absence of human thymus tissue, all EBV infected mice developed
polyclonal B cell lymphomas (some with type III viral latency and some with EBNA2+, LMP1-neg.
tumors), and wildtype and lytic-defective EBV had similar effects. In the presence of co-transplanted
human thymic tissue, approximately half of the animals (6/11) infected with wt virus developed
lymphomas. In contrast only 13% (2/15) of animals infected with lytic-defective virus had tumors.
Tumors were a mixture of type III, type II and type I (both polyclonal and monoclonal). In animals
without lymphoma, EBER+ B cells with type I latency were found in similar numbers, and similar
locations (including lymph nodes, spleen, kidney, omentum, lung, peri-nasal lymphoid tissue, and bone
marrow), in wt and mutant virus infected animals, and rare cells expressed EBNA2. In wt virus-infected
animals, rare BZLF1-expressing cells were found in B cells, as well CD68-positive monocytes. These
results suggest that 1) the presence of co-transplanted human thymic tissue helps human T cells to control
EBV infection in this new mouse model, and 2) lytic EBV infection is not absolutely required for
development of B cell lymphomas in this model, at least when a relatively high titer of virus is
administered, but may contribute in the presence of the thymus.
EBV Conference 2008 Guangzhou
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