title: Complement and HIV-I infection/HIV-associated neurocognitive disorders.
abstract: The various neurological complications associated with HIV-1 infection, specifically HIV-associated neurocognitive disorders (HAND) persist as a major public health burden worldwide. Despite the widespread use of anti-retroviral therapy, the prevalence of HAND is significantly high. HAND results from the direct effects of an HIV-1 infection as well as secondary effects of HIV-1-induced immune reaction and inflammatory response. Complement, a critical mediator of innate and acquired immunity, plays important roles in defeating many viral infections by the formation of a lytic pore or indirectly by opsonization and recruitment of phagocytes. While the role of complement in the pathogenesis of HIV-1 infection and HAND has been previously recognized for over 15 years, it has been largely underestimated thus far. Complement can be activated through HIV-1 envelope proteins, mannose-binding lectins (MBL), and anti-HIV-1 antibodies. Complement not only fights against HIV-1 infection but also enhances HIV-1 infection. In addition, HIV-1 can hijack complement regulators such as CD59 and CD55 and can utilize these regulators and factor H to escape from complement attack. Normally, complement levels in brain are much lower than plasma levels and there is no or little complement deposition in brain cells. Interestingly, local production and deposition of complement are dramatically increased in HIV-1-infected brain, indicating that complement may contribute to the pathogenesis of HAND. Here, we review the current understanding of the role of complement in HIV-1 infection and HAND, as well as potential therapeutic approaches targeting the complement system for the treatment and eradications of HIV-1 infection.
authors.affiliation: Department of Neuroscience, Temple University School of Medicine, Room# 749, 3500 N Broad Street, Philadelphia, PA, 19140, USA.
authors.forename: Fengming
authors.initials: F
authors.lastname: Liu
authors.forename: Shen
authors.initials: S
authors.lastname: Dai
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gordon
authors.forename: Xuebin
authors.initials: X
authors.lastname: Qin
mesh_terms: D015526:AIDS Dementia Complex / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000821:virology; D056704:Adaptive Immunity; D000914:Antibodies, Viral / Q000097:blood*; D000936:Antigen-Antibody Complex / Q000097:blood; D015703:Antigens, CD / Q000276:immunology; D003165:Complement System Proteins / Q000378:metabolism*; D015483:HIV Antibodies / Q000097:blood*; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D037241:Mannose-Binding Lectins / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D015483:HIV Antibodies; D037241:Mannose-Binding Lectins; D014759:Viral Envelope Proteins; D003165:Complement System Proteins