Complement mediates the binding of HIV to erythrocytes

J Immunol. 2004 Sep 15;173(6):4236-41. doi: 10.4049/jimmunol.173.6.4236.

Abstract

A fraction of HIV is associated with erythrocytes even when the virus becomes undetectable in plasma under antiretroviral therapy. The aim of the present work was to further characterize this association in vitro. We developed an in vitro model to study the factors involved in the adherence of HIV-1 to erythrocytes. Radiolabeled HIV-1 (HIV) and preformed HIV-1/anti-HIV immune complexes (HIV-IC) were opsonized in various human sera, purified using sucrose density gradient ultracentrifugation, and incubated with human erythrocytes. We observed that, when opsonized in normal human serum, not only HIV-IC, but also HIV, bound to erythrocytes, although the adherence of HIV was lower than that of HIV-IC. The adherence was abolished when the complement system was blocked, but was maintained in hypogammaglobulinemic sera. Complement-deficient sera indicated that both pathways of complement were important for optimal adherence. No adherence was seen in C1q-deficient serum, and the adherence of HIV was reduced when the alternative pathway was blocked using anti-factor D Abs. The adherence could be inhibited by an mAb against complement receptor 1. At supraphysiological concentrations, purified C1q mediated the binding of a small fraction of HIV and HIV-IC to erythrocytes. In conclusion, HIV-IC bound to erythrocytes as other types of IC do when exposed to complement. Of particular interest was that HIV alone bound also to erythrocytes in a complement/complement receptor 1-dependent manner. Thus, erythrocytes may not only deliver HIV-IC to organs susceptible to infection, but free HIV as well. This may play a crucial role in the progression of the primary infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinemia / blood
  • Agammaglobulinemia / immunology
  • Agammaglobulinemia / virology
  • Antigen-Antibody Complex / blood
  • Binding Sites, Antibody
  • Cell Adhesion / immunology
  • Cell Line
  • Complement C1q / physiology
  • Complement Pathway, Alternative / immunology
  • Complement System Proteins / physiology*
  • Dose-Response Relationship, Immunologic
  • Erythrocytes / immunology*
  • Erythrocytes / metabolism
  • Erythrocytes / virology*
  • HIV Antibodies / blood
  • HIV Antigens / blood
  • HIV Antigens / immunology
  • HIV-1 / immunology*
  • HIV-1 / metabolism
  • Humans
  • Immune Adherence Reaction
  • Immune Sera / metabolism
  • Receptors, Complement 3b / physiology

Substances

  • Antigen-Antibody Complex
  • HIV Antibodies
  • HIV Antigens
  • Immune Sera
  • Receptors, Complement 3b
  • Complement C1q
  • Complement System Proteins