Abstract:
SIVmac causes an immune deficiency syndrome in Asian macaques that is very similar to AIDS in man. Like HIV, SIV induces encephalitis characterized by perivascular infiltrates of macrophages and giant cells. The perivascular localization of these signature histopathologic lesions strongly suggests that the virus enters the neuropil through the blood-brain-barrier (BBB). Detection of SIV RNA by reverse transcriptase in situ polymerase chain reaction demonstrated viral RNA both in perivascular macrophage-like cells and in cells lining the blood vessel itself, which corresponded morphologically to endothelial cells. The purpose of this study was to determine the in vitro susceptibility of macaque brain microvessel endothelial cells (MBMEC), the most important cellular components of the BBB, to SIV infection. Primary macaque brain microvessel endothelial cells were isolated and maintained in culture as confluent monolayers of cells which stained positive for Factor VIII-related antigen, an endothelial cell-specific marker. MBMEC were inoculated with either SIVmac239/17E-Br, a macrophage-tropic, neurovirulent strain, or SIVmac239, a lymphocyte-tropic, non-neurovirulent strain. Cultures inoculated with SIVmac239/17E-Br were determined to be productively infected as measured by: development of cytopathic effect, PCR to detect viral DNA, in situ hybridization for viral RNA, immunocytochemistry for viral antigen, double labeling for Factor VIII-related antigen and viral RNA, and titration of virus in cell-free supernatants. Parallel cultures of MBMEC inoculated with SIVmac239 were not infected. These findings suggest that endothelial cell tropism may contribute to neurovirulence. Endothelial cell infection, in addition to increasing viral load in the CNS, may alter BBB integrity and contribute to CNS dysfunction.
Keywords: Animal Antigens, Viral/ANALYSIS AIDS Dementia Complex/PHYSIOPATHOLOGY Brain/BLOOD SUPPLY/PATHOLOGY Cells, Cultured Encephalitis/ETIOLOGY/*PHYSIOPATHOLOGY Endothelium, Vascular/*MICROBIOLOGY/PATHOLOGY Human Immunohistochemistry In Situ Hybridization Macaca Macrophages/MICROBIOLOGY Microcirculation/*MICROBIOLOGY/PATHOLOGY RNA, Viral/ANALYSIS Simian Acquired Immunodeficiency Syndrome/*COMPLICATIONS/ PHYSIOPATHOLOGY SIV/*ISOLATION & PURIF ABSTRACT 940730
M9470907
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