Blood, Vol. 94 No. 6 (September 15), 1999:
pp. 2090-2101
A Novel Epstein-Barr Virus-Like Virus, HVMNE, in a
Macaca Nemestrina With Mycosis Fungoides
E.D. Rivadeneira,
M.G. Ferrari,
R.F. Jarrett,
A.A. Armstrong,
P. Markham,
T. Birkebak,
S. Takemoto,
C. Johnson-Delaney,
J. Pecon-Slattery,
E.A. Clark, and
G. Franchini
From the National Cancer Institute, Basic Research Laboratory,
Bethesda, MD; the Leukaemia Research Fund Virus Centre, Department of
Veterinary Pathology, University of Glasgow, Glasgow, UK; the Advanced
Biotechnology Laboratory, Rockville, MD; the Department of Comparative
Medicine and the Washington Regional Primate Research Center,
University of Washington, Seattle, WA; and the Frederick Cancer
Research Development Center, National Cancer Institute, Frederick, MD.
Epstein-Barr virus (EBV) infection of humans has been associated
with the development of lymphoid malignancies mainly of B-cell lineage,
although occasionally T-cell lymphomas have been reported. We describe
here the characterization of a novel EBV-like virus (HVMNE)
isolated from a simian T-cell lymphotropic virus type I/II (STLV-I/II)
seronegative pigtailed macaque (Macaca nemestrina) with a
cutaneous T-cell lymphoma. Immunohistochemistry studies on the skin
lesions demonstrated that the infiltrating cells were of the
CD3+/CD8+ phenotype. Two primary
transformed CD8+ T-cell lines were obtained from cultures
of peripheral blood mononuclear cells (PBMC) and skin, and, with time,
both cell lines became interleukin-2-independent and acquired the
constitutive activation of STAT proteins. Polymerase chain reaction
analysis of the DNA from the cell lines and tissues from the
lymphomatous animal demonstrated the presence of a 536-bp DNA fragment
that was 90% identical to EBV polymerase gene sequences, whereas the same DNA was consistently negative for STLV-I/II sequences. Electron microscopy performed on both cell lines, after sodium butyrate treatment, showed the presence of a herpes-like virus that was designated HVMNE according to the existing nomenclature. In
situ hybridization studies using EBV Epstein-Barr viral-encoded RNA probes showed viral RNA expression in both CD8+ T-cell
lines as well as in the infiltrating CD8+ T cells of
skin-tissue biopsies. Phylogenetic analysis of a 465-bp fragment from
the polymerase gene of HVMNE placed this virus within the
Lymphocryptovirus genus and demonstrated that HVMNE
is a distinct virus, clearly related to human EBV and other EBV-like
herpesviruses found in nonhuman primates.
