title: A novel approach to inhibit HIV-1 infection and enhance lysis of HIV by a targeted activator of complement.
abstract: BACKGROUND
  The complement system is one of the most potent weapons of innate immunity. It is not only a mechanism for direct protection against invading pathogens but it also interacts with the adaptive immunity to optimize the pathogen-specific humoral and cellular defense cascades in the body. Complement-mediated lysis of HIV is inefficient but the presence of HIV particles results in complement activation by the generation of many C3-fragments, such as C3dg and C3d. It has been demonstrated that activation of complement can enhance HIV infection through the binding of special complement receptor type 2 expression on the surface of mature B cells and follicular dendritic cells.
  
  
  OBJECTIVE
  Previous studies have proven that the complement-mediated antibody-dependent enhancement of HIV infection is mediated by the association of complement receptor type 2 bound to the C3 fragment and deposited on the surface of HIV virions. Thus, we hypothesize that a new activator of complement, consisting of a target domain (C3-binding region of complement receptor type 2) linked to a complement-activating human IgG1 Fc domain (CR2-Fc), can target and amplify complement deposition on HIV virions and enhance the efficiency of HIV lysis.
  
  
  METHODS
  Our hypothesis was tested using cell-free HIV-1 virions cultivated in vitro and assessment of virus opsonization was performed by incubating appropriate dilutions of virus with medium containing normal human serum and purified CR2-Fc proteins. As a control group, viruses were incubated with normal human serum under the same conditions. Virus neutralization assays were used to estimate the degree of CR2-Fc-enhanced lysis of HIV compared to untreated virus.
  
  
  CONCLUSIONS
  The targeted complement activator, CR2-Fc, can be used as a novel approach to HIV therapy by abrogating the complement-enhanced HIV infection of cells.
authors: Institute of Disease Control and Prevention, Academy of Military Medical Science, Beijing, PR China. xyy_827@sina.com
authors: Yuanyong
authors: Y
authors: Xu
authors: Chuanfu
authors: C
authors: Zhang
authors: Leili
authors: L
authors: Jia
authors: Cuirong
authors: C
authors: Wen
authors: Huihui
authors: H
authors: Liu
authors: Yong
authors: Y
authors: Wang
authors: Yansong
authors: Y
authors: Sun
authors: Liuyu
authors: L
authors: Huang
authors: Yusen
authors: Y
authors: Zhou
authors: Hongbin
authors: H
authors: Song
mesh_terms: D003176:Complement C3 / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D007141:Immunoglobulin Fc Fragments / Q000276:immunology* / Q000378:metabolism; D050296:Microbial Viability; D009500:Neutralization Tests; D017464:Receptors, Complement 3d / Q000276:immunology* / Q000378:metabolism
chemical_list: D003176:Complement C3; D007141:Immunoglobulin Fc Fragments; D017464:Receptors, Complement 3d