Progressive multifocal leukoencephalopathy and oligodendroglioma in a monkey co-infected by simian immunodeficiency virus and simian virus 40.
A rhesus monkey experimentally inoculated with simian immunodeficiency virus (SIV) mac251 was killed 42 months later because of poor general condition. CD4 lymphocyte count which was 3,430/mm3 before inoculation, had decreased to 638/mm3 2 months before death. Neuropathological examination revealed changes characteristic of progressive multifocal leukoencephalopathy (PML) in the white matter of the cerebral hemispheres and brain stem. In situ hybridization was negative for JC virus but markedly positive for simian virus 40 (SV40) in the nuclei of many oligodendrocytes. Many oligodendrocytes also expressed p53. Within an area involved by PML, there was a densely cellular tumor with honeycomb appearance and elongated vessels characteristic of oligodendrogliomas. Within the tumor in situ hybridization for SV40 and immunocytochemistry for p53 were negative. Opportunistic infection by SV40 has been occasionally reported in experimentally SIV-infected monkeys resulting in PML or malignant astrocytoma. Association of JC virus-induced PML and astrocytomas has been reported in three human cases without AIDS. In those cases, as in our monkey, polyomaviruses (SV40 or JC virus) were expressed in the areas with PML but not in the glial tumor. Association of PML and oligodendroglioma has not been reported previously to our knowledge. The relationship between oligodendrocyte proliferation and polyomavirus infection of oligodendrocytes is unclear. Our findings suggest that binding of the viral protein to p53 may result in inactivation of the pro-apoptotic protein favoring the proliferation of a randomly occurring tumoral clone of oligodendrocytes.
Chrétien
F
F
Laboratoire de Neuropathologie, Hôpital Raymond Poincaré-Faculté de Médecine Paris-Ouest, Garches, France.
Boche
D
D
Lorin de la Grandmaison
G
G
Ereau
T
T
Mikol
J
J
Hurtrel
M
M
Hurtrel
B
B
Gray
F
F
D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology*; D001932:Brain Neoplasms / Q000473:pathology / Q000821:virology*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000150:complications / Q000473:pathology / Q000821:virology*; D008254:Macaca nemestrina / Q000033:anatomy & histology / Q000821:virology*; D009837:Oligodendroglioma / Q000150:complications / Q000473:pathology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*; D013539:Simian virus 40 / Q000472:pathogenicity*