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Novel role of MBL in HIV-1 related neuroinflammation and CNS impairment in methamphetamine users

  • Author(s): Geffen, Brent Jacob
  • et al.
Abstract

Methamphetamine (METH) is a highly addictive neurotoxic psychostimulant abused commonly by individuals infected by human immunodeficiency virus (HIV). METH enhances HIV-1 replication in vitro. HIV-1 infection and METH use cause synergistic neuronal death and neurotoxicity via oxidative stress and inflammatory immune response. Mannose binding lectin (MBL), an innate immune protein, binds HIV-1 envelope protein gp120 and activates the complement pathway for HIV-1 opsonization and phagocytosis. Dr. Singh's lab has reported increased MBL expression in HIV encephalitis (HIVE) suggesting MBL-mediated neuroinflammation. Our hypothesis is that METH enhances lectin complement pathway (LCP) protein expression and activation; which are associated with neuroinflammation and immune complex formation. Additionally we hypothesize that this increased LCP activation is associated with meth -enhanced viral replication and increased expression of HIV co-receptors. Our results show that METH significantly enhances MBL expression and LCP activation via MBL-C3d deposition in HIV-infected brain. MBL expression was associated with viral proteins p24 and gp120, and co- localized with HIV co-receptors CCR5 and CXCR4 with higher expression in METH+ HIV+ compared to METH- HIV+ cases which also displayed higher neuroinflammation as marked by increased MCP-1 expression

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