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

Abstract

HV(MNE) 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 HV(MNE)-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) 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. HV(MNE) 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 HV(MNE) DNA, expression of an LMP1-like protein, and acquisition of interleukin-2 independence, and constitutive activation of the Jak/STAT pathway. Thus, HV(MNE) 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.