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Expression of major histocompatibility complex antigens and serum neutralizing antibody in murine retroviral
R M Nagra1, P K Wong, C A Wiley
1Department of Pathology, School of Medicine, University of California, San Diego, La Jolla 92093-0612.
Abstract:
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.
Insights
Murine leukemia virus infection causes central nervous system (CNS) degeneration. Viral spread and cell tropism varied between strains, with limited immune response potentially hindering immunotherapy for CNS retroviral infections.
Area of Science:
- Neurovirology
- Immunology
- Central Nervous System (CNS) Research
Background:
- Murine leukemia virus (MLV) infection models noninflammatory CNS degeneration.
- Understanding MLV pathogenesis is crucial for developing treatments for CNS retroviral infections.
Purpose of the Study:
- To compare the neuropathogenesis of two MLV strains (pNE-8 and ts-1).
- To investigate the role of Major histocompatibility complex (MHC) expression in MLV infection and persistence within the CNS.
- To identify factors associated with protection from lethal MLV infection.
Main Methods:
- Infection of mice with molecularly cloned MLV strains pNE-8 and ts-1.
- Monitoring viral spread, tropism (endothelial cells, oligodendrocytes, neurons, macrophages/microglia, astrocytes), and neuropathology.
- Assessing Major histocompatibility complex (MHC) class I (beta 2-microglobulin) and class II expression in infected CNS tissues.
- Quantifying serum neutralizing antibody titers in infected mice.
Main Results:
- The ts-1 MLV strain spread twice as rapidly and ascended higher in the neuraxis compared to pNE-8.
- Endothelial cells, oligodendrocytes, and neurons were infected; astrocytes were not. Macrophages/microglia were also infected by ts-1.
- Elevated MHC class I expression was observed in ts-1 infected endothelial cells and later in macrophages/microglia. Limited MHC expression was noted overall.
- Mice escaping lethal infection exhibited higher neutralizing antibody titers and no detectable CNS virus or neuropathology.
Conclusions:
- Differential viral spread and tropism influence MLV neuropathogenesis.
- Limited intra-CNS MHC expression may contribute to viral persistence and poses a challenge for immunotherapy.
- High neutralizing antibody titers appear protective against lethal MLV infection and CNS damage.