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Cell association of HIV in AIDS-related encephalopathy and dementia
A Porwit1, C Parravicini, A L Petren
1Dept. of Pathology, Karolinska Hospital, Stockholm, Sweden.
Abstract:
The presence of HIV gag and env proteins (HIV Ag) and virus replicating cells was studied by immunohistochemistry and in situ hybridization, respectively, in brain specimens from five HIV infected patients. HIV antigens were detected in 3 of 5 brains in micronodular areas characterized by increased cellularity and the presence of multinuclear giant cells. By double immunostaining, HIV Ag positive cells were shown to express markers common to macrophages and microglia i.e. Leu M5+, My4+, HLA-Dr+, RCA-1+, and to a lesser extent CD4+ (Leu3+). Another macrophage specific marker, KiM6, was found only on HIV+ cells in HIV infected specimens and not in uninfected, control brains. Medium-sized, virus replicating cells were found exclusively in micronodular areas, but in much smaller quantities than HIV Ag+ cells. Our observations provide further evidence to support the hypothesis that macrophages play an important role in CNS infection by HIV and additionally support the concept that reactive microglial originate from activated macrophages infiltrating the brain. Both direct effects of viral components and cell mediated reactions can be implicated from our findings as mechanisms involved in the pathogenesis of the CNS lesions.
Insights
Macrophages and microglia are key players in central nervous system (CNS) infection by human immunodeficiency virus (HIV). This study identifies HIV antigens in brain cells, supporting their role in HIV-related CNS disease.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Central nervous system (CNS) complications are common in HIV infection.
- The cellular mechanisms underlying HIV-induced CNS pathology are not fully understood.
Purpose of the Study:
- To investigate the presence and cellular localization of HIV antigens and replicating virus in brain tissue from HIV-infected individuals.
- To elucidate the role of macrophages and microglia in HIV CNS infection.
Main Methods:
- Immunohistochemistry and in situ hybridization were used to detect HIV antigens and replicating virus in brain specimens.
- Double immunostaining was employed to identify cell types expressing HIV antigens.
Main Results:
- HIV antigens (HIV Ag) were detected in 3 of 5 HIV-infected brains, primarily in micronodular areas with multinuclear giant cells.
- HIV Ag-positive cells expressed markers of macrophages and microglia (Leu M5+, My4+, HLA-Dr+, RCA-1+, CD4+).
- Virus-replicating cells were found in smaller quantities than HIV Ag+ cells, exclusively in micronodular areas.
Conclusions:
- Macrophages play a significant role in CNS infection by HIV.
- Reactive microglia in HIV-infected brains may originate from infiltrating activated macrophages.
- Both direct viral effects and cell-mediated immune responses contribute to HIV-related CNS lesion pathogenesis.