INHIBITION OF HIV-1 INFECTION IN-VITRO BY MONOCLONAL-ANTIBODIES TO THE COMPLEMENT RECEPTOR-TYPE-3 (CR3) - AN ACCESSORY ROLE FOR CR3 DURING VIRUS ENTRY

Adhesion molecules are known to contribute to infectivity of HIV-1. He re we tested whether the complement receptor type 3 (CR3, CD11b), an a lpha(m) beta(2) integrin, plays an accessory role in the infection pro cess of HIV-1, because ICAM-1, a ligand of CR3, is present on the enve lope of HIV-1. In addition, the viral transmembrane protein gp41 share s four regions of homology with the complement component C3, a further CR3 ligand. Infection of PBMCs with HIV-IIIB and primary isolates was partially inhibited by anti-CR3 antibodies. A peptide derived from th e complement component C3, covering the CR3-binding site of C3 and sha ring strong similarity to the immunosuppressive region of gp41; signif icantly reduced the HIV-1 titer in infection assays. Recombinant solub le gp41 (rsgp41) and the peptide covering the immunosuppressive domain of gp41 inhibited the resetting of iC3b-coated sheep erythrocytes wit h U937 via complement receptors (CRs) with an efficiency comparable to monoclonal anti-CR antibodies. In addition, sub-populations of CD4 and CD8 + T-cells isolated from HIV-infected individuals were found to upregulate CR3 as determined by FACS analysis and on the mRNA level. Since gp41 has been implicated in viral fusion, an interaction of its C3-homology region in gp41 or an interaction of ICAM on the surface of free virus with CRs might contribute to facilitate viral entry. (C) 1 998 Elsevier Science Ltd. All rights reserved.