HVMNE, a novel lymphocryptovirus related to Epstein-Barr virus, induces lymphoma in New Zealand White rabbits

HVMNE is a novel Epstein-Barr (EBV)-like virus Isolated from a Macaca nemes trina with CD8(+) T-cell mycosis fungoidescutaneous T-cell lymphoma. Here i t Is demonstrated that intravenous inoculation of irradiated HVMNE-infected T cells or cell-free virus from the J94356(PBMC) cell line In New Zealand White rabbits results In seroconversion to the viral capsid antigen (VCA) o f EBV; all animals that seroconverted to VCA developed malignant lymphoma w ithin months of inoculation. In contrast, control rabbits, inoculated with heat-inactivated culture supernatants from the same cell line, failed to se roconvert to VCA and did not develop disease. Disseminated lymphoma cells o f mixed origin were detected in most vital organs, including the spleen, li ver, lungs, kidneys, and heart of the affected rabbits. Neoplastic infiltra tes were also observed in lymph nodes, thymus, skin, and subcutaneous tissu es. HVMNE DNA and EBV-like RNA expression was demonstrated in the lymphomat ous organs and in 2 transformed T-cell lines, one established from the lymp h 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, ex pression of an LMP1-like protein, and acquisition of interleukin-2 independ ence, and constitutive activation of the Jak/STAT pathway. Thus, HVMNE in r abbits provides a valuable animal model for human T-cell lymphoma whereby g enetic determinants for T-cell transformation by this EBV-like animal virus can be studied. (C) 2001 by The American Society of Hematology.