title: Mechanism for complement-mediated, antibody-dependent enhancement of human immunodeficiency virus type 1 infection in MT2 cells is enhanced entry through CD4, CD21, and CXCR4 chemokine receptors.
abstract: Some antibodies neutralize Human Immunodeficiency Virus (HIV). However, antibody to HIV and complement can enhance HIV replication if cells express both complement receptors and CD4, a phenomenon described as complement-mediated, antibody-dependent enhancement (C'ADE). Although increased binding of opsonized virions has been reported, the mechanism by which C'ADE enhances HIV replication remains unproven. In this study, real-time polymerase chain reaction to detect HIV cDNA indicates that complement and anti-HIV antibodies enhance HIV entry 8- to 30- fold with similar increases in integrated provirus. Thus, complement increases HIV replication through a mechanism of enhanced entry. To further refine the mechanism of C'ADE, chemokine receptor antagonists were employed. JM2987, a CXCR4 chemokine receptor antagonist, blocked HIV infection and C'ADE; thus CD4, complement receptors, and CXCR4 chemokine receptors are required for enhanced entry of HIV into MT2 cells. Finally, anti-HIV immunoglobulin enhanced replication of not only group M clade B HIV but also group M clade D and group O isolates. These data demonstrate that antibodies mediating C'ADE of HIV infection are broadly reactive.
authors.affiliation: Department of Pathology, University of California, Irvine, CA 92697-4800, USA. ewrobins@uci.edu
authors.forename: W Edward
authors.initials: WE
authors.lastname: Robinson
mesh_terms: D019067:Antibody-Dependent Enhancement; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D003165:Complement System Proteins / Q000378:metabolism*; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D019718:Receptors, CXCR4 / Q000378:metabolism*; D017464:Receptors, Complement 3d / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D015483:HIV Antibodies; D019718:Receptors, CXCR4; D017464:Receptors, Complement 3d; D003165:Complement System Proteins