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Serial pathogenesis study of SIV brain infection
L R Sharer1, J Michaels, M Murphey-Corb
1New Jersey Medical School, Newark.
Abstract:
A serial study of early SIV brain infection revealed initial involvement of leptomeninges, followed by perivascular infection of brain parenchyma. Severity of SIV encephalitis correlated with severity of systemic disease rather than with length of infection. Diffuse white matter disease was not observed, and there was little evidence of SIV infection of brain endothelial cells. SIV infection of leptomeninges is separate from infection of the brain, which appears to be due to transvascular spread of infected monocytes/macrophages.
Insights
Early simian immunodeficiency virus (SIV) brain infection primarily affects the leptomeninges and perivascular areas. SIV encephalitis severity links to systemic illness, not infection duration, with monocytes/macrophages driving brain spread.
Area of Science:
- Neurology
- Virology
- Immunology
Background:
- Simian immunodeficiency virus (SIV) is a model for human immunodeficiency virus (HIV) infection.
- Understanding SIV neuropathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the temporal and spatial patterns of early SIV brain infection.
- To determine factors correlating with SIV encephalitis severity.
Main Methods:
- Serial examination of SIV-infected brains.
- Histopathological analysis to identify viral distribution and cellular involvement.
Main Results:
- Early SIV infection involved the leptomeninges and perivascular parenchyma.
- SIV encephalitis severity correlated with systemic disease, not infection duration.
- Minimal SIV infection of brain endothelial cells and no diffuse white matter disease were observed.
- Leptomeningeal and brain infections appeared distinct, with monocytes/macrophages mediating brain entry.
Conclusions:
- SIV brain infection follows a specific pattern, starting in the meninges and spreading perivascularly.
- Systemic disease severity is a key determinant of SIV encephalitis.
- Monocyte/macrophage trafficking is a primary route for SIV entry into the brain parenchyma.