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.
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.
Robinson
W Edward
WE
Department of Pathology, University of California, Irvine, CA 92697-4800, USA. ewrobins@uci.edu
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
D015704:CD4 Antigens; D015483:HIV Antibodies; D019718:Receptors, CXCR4; D017464:Receptors, Complement 3d; D003165:Complement System Proteins