Expression of major histocompatibility complex antigens and serum neutralizing antibody in murine retroviral encephalitis.
Murine leukemia virus infection serves as a model for noninflammatory degeneration of the central nervous system (CNS). During the course of infection with either of the molecularly cloned viruses pNE-8 or ts-1, we observed that ts-1 spread twice as rapidly as pNE-8, and ascended higher in the neuraxis. Endothelial cells were infected first, followed by oligodendrocytes and neurons, while astrocytes containing glial fibrillary acidic protein were not infected. Additionally, ts-1 also infected macrophages/microglia. Major histocompatibility complex (MHC) class I beta 2-microglobulin expression was minimal in pNE-8 infected mice, while it was elevated in endothelial cells of early ts-1 lesions, and in macrophages/microglia during later stages. Occasional infected cells expressed beta 2-microglobulin while rare endothelial and parenchymal cells expressed MHC class II in both viral infections. Limited intra-CNS MHC expression may be one of the mechanisms of viral persistence and will present a barrier to developing immunotherapy for CNS retroviral infections. The few mice that escaped lethal infection had higher serum titers of neutralizing antibodies and showed no neuropathologic changes or detectable virus in the CNS. Higher titers of neutralizing antibodies may protect the CNS from infection.
Nagra
R M
RM
Department of Pathology, School of Medicine, University of California, San Diego, La Jolla 92093-0612.
Wong
P K
PK
Wiley
C A
CA
D000818:Animals; D000831:Animals, Newborn; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood*; D001921:Brain / Q000276:immunology / Q000473:pathology*; D003001:Cloning, Molecular; D004660:Encephalitis / Q000276:immunology / Q000473:pathology*; D005622:Friend murine leukemia virus; D015870:Gene Expression; D005802:Genes, MHC Class II; D009052:Leukemia Virus, Murine; D007942:Leukemia, Experimental / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D008264:Macrophages / Q000473:pathology; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008979:Moloney murine leukemia virus; D009367:Neoplasm Staging; D009500:Neutralization Tests; D014412:Tumor Virus Infections / Q000276:immunology / Q000473:pathology*; D001613:beta 2-Microglobulin / Q000096:biosynthesis / Q000235:genetics
D000914:Antibodies, Viral; D001613:beta 2-Microglobulin