Anti-MIP-1alpha and anti-RANTES antibodies: new allies of HIV-1?
The human immunodeficiency virus type 1 was recently found to use several chemokine receptors in addition to the CD4 molecule for attachment to, and fusion with, CD4+ cells. The interaction between macrophage-tropic HIV-1 strains and one of these chemokine receptors, CCR5, was shown to involve the V3-loop of the viral envelope glycoprotein gp120. Physiological ligands of CCR5, namely the beta-chemokines MIP-1alpha, MIP-1beta, and RANTES, were found to competitively inhibit the V3-loop-CCR5 interaction. We therefore hypothesized that the V3-loop of gp120 of macrophage-tropic HIV-1 may share a binding site on CCR5 with MIP-1alpha, MIP-1beta, and RANTES and that the V3-loop therefore might have some homology with these beta-chemokines. In the present study, we could demonstrate that affinity purified anti-V3-loop antibodies isolated from serum of an HIV-1-infected patient bound to MIP-1alpha and RANTES. Furthermore, sera of HIV-infected hemophilia patients without AIDS or ARC had significantly higher anti-MIP-1alpha and anti-RANTES antibody activities than sera of HIV-infected hemophilia patients with AIDS. We speculate that the higher activities of anti-MIP-1alpha and anti-RANTES antibodies in asymptomatic HIV-1 infected individuals might be due to a cross-reaction of beta-chemokines with anti-V3-loop antibodies raised against gp120 of macrophage-tropic HIV-1 strains, known to be prevailing in the asymptomatic stage of HIV infection. Such anti-chemokine antibodies may play a deleterious role in the pathogenesis of AIDS by reducing the chemokines' potential to inhibit HIV-1 entry into CD4+ cells.
Kissler
S
S
Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
Süsal
C
C
Opelz
G
G
D000386:AIDS-Related Complex / Q000097:blood; D000163:Acquired Immunodeficiency Syndrome / Q000097:blood; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000276:immunology*; D003429:Cross Reactions; D015658:HIV Infections / Q000097:blood; D015497:HIV-1; D006467:Hemophilia A / Q000097:blood; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008213:Lymphocyte Activation; D019402:Macrophage Inflammatory Proteins / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D007074:Immunoglobulin G; D019402:Macrophage Inflammatory Proteins