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|Publication Abstract Display|
|Type: Published Abstract|
|Title: Increased expression of complement receptor 2 and ligand C3 deposition in HIV encephalitis: A potential link to innate and adaptive immune responses in NeuroAIDS.|
|Authors: Nathamu S, Adame A, Dumaop W, Gouaux B, Moore D, Masliah E, Singh K, and the HNRC Group|
|Publication: 19th Conference on Retroviruses and Opportunistic Infections|
|Volume: Issue: Pages: |
|Abstract:Background: Complement receptor 2 (CR2 or CD21), is a receptor to B cells and the complement component 3 final degradation product C3d. This receptor/ligand interaction results in formation of a formidable CR2/C3d complex to eliminate the foreign antigens. A novel role of CR2 in CD4-independent binding to HIV-1 and in enhancement of HIV infection in lymphoid tissue has been reported. We hypothesized that an altered expression of CR2 and its ligand C3d in HIV-1 infected brain is associated with the neuroinflammatory responses and HIV encephalitis (HIVE).
Methods: Expression and co-localization of CR2, C3d, monocyte chemoattractant protein-1 (MCP-1), and brain cell markers in the frontal cortex of the post-mortem brain tissues from HIV- healthy controls (n=5) and those with and without HIVE (n=15 each) were evaluated by immunofluorescence, confocal microscopy and western blot analyses. Paired t test was used to compare expression of MBL and related proteins in HIVE vs. HIV+ non-HIVE or HIV- cases. Human brain tissues were obtained from the California NeuroAIDS Tissue Network.
Results: Our results showed a twofold increase and co-localization of CR2 and C3d positive cells in HIVE vs. non-HIVE cases (p=0.01). An overall increase of CR2 and C3d in microglia, neurons, astrocytes and oligodendrocytes in HIVE vs. non-HIVE cases (p=0.0001) was observed. Also there was a twofold increase in the expression of neuroinflammatory marker MCP-1 in HIVE vs. non-HIVE cases (p=0.0001) and it also co-localized with CR2/C3d complex. Importantly, a significantly increased expression and co-localization of HIV-1 gp120 or gp41 proteins with CR2/C3d was detected in HIVE vs. non-HIVE cases (p=0.0012). No differential expression of studied markers was observed in HIV negative healthy controls.
Conclusions: Higher expression of CR2 and increased deposition of its ligand C3d in association with MCP-1 and viral gp120/gp41 proteins, suggest that CR2/C3d interaction play an important role in HIV-1 related neuroinflammation and encephalitis.|
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