UC San Diego

Human immunodeficiency virus-1 (HIV-1) is a life- threatening virus which disrupts host immune system, and about half of the HIV-1 infected individuals develop neurocognitive impairment in brain. Neuronal autoimmunity is also observed in patients with HIV-1 infection, resulting in inflammation and damage in neurons and axons. Mannose binding lectin, MBL, plays important role in HIV by its direct binding of gp120, envelope protein present on the surface of HIV-1through lectin mediated complement activation pathway. MBL is also associated with initiation of autoimmunity due to its involvement in clearance of apoptotic cells. This study focuses on determining the role of MBL mediated complement pathway in the induction of neuronal autoimmunity during HIV-1 infection of the brain. Overall, higher MBL/gp120 immune complex deposition, and MBL/gp120 interaction with axonal damage marker amyloid precursor protein (APP) in HIV encephalitis (HIVE) brain suggest MBL mediated neuroinflammation and neuronal damage in HIVE. Increased immunoreactivitv of MBL/gp120 immune complex with myelin oligodendrocyte glycoprotein (MOG), and myelin basic protein (MBP) suggest that these interactions potentially damage oligodendrocytes and interfere with myelination in HIVE. Increased deposition of MBL mediated immune complexes (C3d,C5b9,IgG) in HIVE suggests that deposition of these aggregates may play a key role in axonal damage, demyelination and neuroinflammation in HIV encephalitis. Presence of C4, C5, and MBL autoantibodies and higher inflammatory cytokine response (IL-1[beta], IL-6, IL-2, and IL-8, Rantes,MIP- 1[beta]2, and MCP-1)in the cerebrospinal fluid (CSF) of HIV-1 infected individuals with neurocognitive impairment suggests that presence of MBL autoantibodies is associated with proinflammatory cytokine immune response in HIV-1 related CNS impairment