ANTI-MIP-1-ALPHA AND ANTI-RANTES ANTIBODIES - NEW ALLIES OF HIV-1

The human immunodeficiency virus type 1 was recently found to use seve ral 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-1 alpha , MIP-1 beta, and RANTES, were found to competitively inhibit the V3-l oop-CCR5 interaction. We therefore hypothesized that the V3-loop of gp 120 of macrophagetropic HIV-1 may share a binding site on CCR5 with MI P-1 alpha, MIP-1 beta, 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 is olated from serum of an HIV-1-infected patient bound to MIP-1 alpha an d RANTES. Furthermore, sera of HIV-infected hemophilia patients withou t AIDS or ARC had significantly higher anti-MIP-1 alpha and anti-RANTE S antibody activities than sera of HIV-infected hemophilia patients wi th AIDS. We speculate that the higher activities of anti-MIP-1 alpha a nd anti-RANTES antibodies in asymptomatic HIV-1 infected individuals m ight be due to a cross-reaction of beta-chemokines with anti-V3-loop a ntibodies raised against gp120 of macrophage-tropic HIV-1 strains, kno wn to be prevailing in the asymptomatic stage of HIV infection. Such a nti-chemokine antibodies may play a deleterious role in the pathogenes is of AIDS by reducing the chemokines' potential to inhibit HIV-1 entr y into CD4(+) cells. (C) 1997 Academic Press.