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NEOPLASIA
From the Basic Research Laboratory, National Cancer
Institute, Bethesda, MD; the Leukaemia Research Fund Virus Centre,
Glasgow, United Kingdom; and the Advanced Bioscience Laboratories,
Kensington, MD.
HVMNE is a novel Epstein-Barr (EBV)-like virus
isolated from a Macaca nemestrina with
CD8+ T-cell mycosis fungoides-cutaneous T-cell lymphoma.
Here it is demonstrated that intravenous inoculation of irradiated
HVMNE-infected T cells or cell-free virus from the
J94356PBMC cell line in New Zealand White rabbits results
in seroconversion to the viral capsid antigen (VCA) of EBV; all animals
that seroconverted to VCA developed malignant lymphoma within months of
inoculation. In contrast, control rabbits, inoculated with
heat-inactivated culture supernatants from the same cell line, failed
to seroconvert to VCA and did not develop disease. Disseminated
lymphoma cells of mixed origin were detected in most vital organs,
including the spleen, liver, lungs, kidneys, and heart of the affected
rabbits. Neoplastic infiltrates were also observed in lymph nodes,
thymus, skin, and subcutaneous tissues. HVMNE DNA and
EBV-like RNA expression was demonstrated in the lymphomatous organs and
in 2 transformed T-cell lines, one established from the lymph node and
the other from the blood of the 2 lymphomatous animals. Analysis of one
of these T-cell lines demonstrated the persistence of HVMNE
DNA, expression of an LMP1-like protein, and acquisition of
interleukin-2 independence, and constitutive activation of the Jak/STAT
pathway. Thus, HVMNE in rabbits provides a valuable animal
model for human T-cell lymphoma whereby genetic determinants for T-cell
transformation by this EBV-like animal virus can be studied. This article has been cited by other articles:
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| Copyright © 2001 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||