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Publication Abstract Display
Type: Published Abstract
Title: MBL-HIV1gp120 immunoreactivity is associated with markers of neuronal injury.
Authors: Teodorof C, Nguyen D, Kadakia N, Maung R, Soontornniyomkij B, Achim CL, Moore D, Masliah E, Kaul M, Singh K
Year: 2015
Publication: 2015 Conference on Retroviruses and Opportunistic Infections
Volume: Issue: Pages:
Abstract:BACKGROUND: Mannose-binding lectin (MBL), an innate immune response protein binds directly to the mannose residues on HIV-1 envelope glycoprotein 120 (gp120) via its carbohydrate recognition domain (CRD) and leads to complement activation and virus opsonization. We hypothesized that MBL-gp120 interactions in HIV-1 infected brain will be associated with neuronal damage. METHODS: HIV-1 infected frontal cortex brain tissues with or without HIV encephalitis (HIVE) (obtained from California NeuroAIDS Tissue Consortium) and hemi-brain sections from wild type (WT) and gp120 transgenic (gp120tg) mice were used to analyze MBL expression and immunoreactivity with somatodendritic marker MAP2, neurodegeneration marker phospho-Tau (pTau), synaptic marker synaptophysin (SYN) and complement activation product C3d. Furthermore, human primary neuronal cultures (HPNs) were treated with 5nM IIIB-gp120 to determine its effects on neuronal damage. Immunohistochemistry, confocal microscopy, z stacking and immunoblotting were used to analyze expression and immunoreactivity of MBL and gp120 with neuronal markers. RESULTS: Presence of immune complexes (ICs) of MBL and gp120 was associated with a loss of neuronal dendrites (MAP2) and SYN puncta; and an increase of pTau immunoreactivity in HIVE vs. non-HIVE brain (N=5 each). Furthermore, complement activation product C3d was associated with immunodeposition of MBL-gp120 ICs in HIVE tissue. In a gp120tg mouse model, MBL isoforms MBL1 and MBL2 formed ICs with gp120; and compared to the WT mice, hemi-brains from gp120tg mice showed a loss of neuronal dendrites (MAP2) and SYN suggesting MBL-gp120 mediated neuronal damage. Also, 5nM IIIB-gp120 treatment of human primary neurons (HPNs) showed clear immunostaining of MBL-gp120 in perinuclear vesicles and MAP2 along neuronal processes within 30min, followed by a loss of MAP2 and SYN, and an increase of pTau by 6hrs. Confocal microscopy orthogonal view via z-stacking and immunoblots clearly confirmed the immunoreactivity of MBL and gp120. CONCLUSIONS: Presence of MBL-gp120 immune complexes was associated with a loss of MAP2 and SYN, and in an increase of pTau and C3d in HIV-1 infected brain, gp120tg mouse model and HPN cultures suggesting a unique role of MBL-gp120 interactions and complement activation in neuronal damage.

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