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Publication Abstract Display
Type: Published Abstract
Title: Novel MBL-beta amyloid interactions in HIV-1 infected brain: Implications for HIV related aging and Alzheimer’s Disease.
Authors: Tran D, Kumar N, Teodorof C, Adame A, Gouaux B, Moore D, Dumaop W, Michael S, Masliah E, Singh K, and the HNRP Group
Year: 2013
Publication: 20th Conference on Retroviruses and Opportunistic Infections
Volume: Issue: Pages:
Abstract:Background: Mannose binding lectin’s (MBL) carbohydrate recognition domain binds to the high-mannose N-linked glycans on the HIV-1 gp120 envelope protein and activates the complement pathway that leads to virus opsonization and phagocytosis. Also, MBL interacts directly with beta amyloid (bA) through its cysteine-rich domains and modulates inflammation. We hypothesized that MBL interactions with both gp120 and bA facilitate immune complex deposition, inflammation and neuronal damage in HIV neuropathogenesis and Alzheimer’s disease (AD). Methods: Human brain frontal cortex tissues were obtained from the California NeuroAIDS Tissue Network and Alzheimer’s Disease Research Center. Double immunofluorescence, confocal microscopy and western blot analyses were used to evaluate the expression and colocalization of MBL, bA, viral gp120 and monocyte chemoattractant protein -1 (MCP-1, a marker of neuroinflammation) in the frontal cortex of the post-mortem brain tissues from HIV negative healthy controls (n=5), those with and without HIV encephalitis (HIVE) (n=15 each) and AD (n=10). Paired t test was used to compare expression of markers in different cases. Results: Expression of MBL and bA were enhanced almost twofold (p<0.01) in HIVE vs. non-HIVE cases. An increased colocalization of MBL and bA (1.5 fold increase, p<0.05) was observed in HIVE vs. non-HIVE cases. This MBL-bA-HIVE link was further enhanced by the colocalization of MBL, bA and gp120 immune complexes (1.7 fold increase, p<0.01) in HIVE vs. non-HIVE cases. Also, almost tenfold increase of MBL-bA complexes was observed in age matched frontal cortex brain tissues from advanced AD patients with braak stage 5 or higher vs. non-AD or lower braak stage (1 or lower) cases (p<0.01). Furthermore, about eightfold increase in MBL-bA-MCP-1 immune complexes was observed in AD vs. non-AD cases (p<0.01). Brain tissues from older individuals with HIVE or AD showed higher MBL-bA deposits compared to younger individuals (p<0.05 each). In addition to MBL, expression of MBL-associated serine protease-2 (MASP-2), which directly initiates lectin complement activation pathway, was also observed in both HIVE and AD brains. Conclusions: Increased expression and colocalization of MBL with gp120 and beta amyloid proteins suggest that their interactions potentially play an essential role in complement mediated immune complex deposition, neuroinflammation and neuronal damage in HIV neuropathogenesis and Alzheimer’s disease.

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