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

Viral Immunol. 2006 Summer;19(3):434-47. doi: 10.1089/vim.2006.19.434.

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.

MeSH terms

  • Antibody-Dependent Enhancement*
  • CD4 Antigens / metabolism
  • CD4-Positive T-Lymphocytes / virology*
  • Cell Line, Transformed
  • Cell Transformation, Viral
  • Complement System Proteins / metabolism*
  • HIV Antibodies / immunology*
  • HIV-1 / immunology
  • HIV-1 / metabolism
  • HIV-1 / pathogenicity*
  • Humans
  • Receptors, CXCR4 / metabolism*
  • Receptors, Complement 3d / metabolism

Substances

  • CD4 Antigens
  • HIV Antibodies
  • Receptors, CXCR4
  • Receptors, Complement 3d
  • Complement System Proteins