RT Journal Article SR Electronic T1 A Peptide Derived from Bee Venom-Secreted Phospholipase A2 Inhibits Replication of T-Cell Tropic HIV-1 Strains via Interaction with the CXCR4 Chemokine Receptor JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 341 OP 347 DO 10.1124/mol.60.2.341 VO 60 IS 2 A1 David Fenard A1 Gerard Lambeau A1 Thomas Maurin A1 Jean-Claude Lefebvre A1 Alain Doglio YR 2001 UL http://molpharm.aspetjournals.org/content/60/2/341.abstract AB We have previously shown that secreted phospholipases A2(sPLA2) from bee and snake venoms have potent anti-human immunodeficiency virus (HIV) activity (Fenard et al., 1999). These sPLA2s block HIV-1 entry into host cells through a mechanism linked to sPLA2 binding to cells. In this study, 12 synthetic peptides derived from bee venom sPLA2(bvPLA2) have been tested for inhibition of HIV-1 infection. The p3bv peptide (amino acids 21 to 35 of bvPLA2) was found to inhibit the replication of T-lymphotropic (T-tropic) HIV-1 isolates (ID50 = 2 μM) but was without effect on monocytotropic (M-tropic) HIV-1 isolates. p3bv was also found capable of preventing the cell-cell fusion process mediated by T-tropic HIV-1 envelope. Finally, p3bv can inhibit the binding of radiolabeled stromal cell-derived factor (SDF)-1α, the natural ligand of CXCR4, and the binding of 12G5, an anti-CXCR4 monoclonal antibody. Taken together, these results indicate that p3bv blocks the replication of T-tropic HIV-1 strains by interacting with CXCR4. Its mechanism of action however appears distinct from that of bvPLA2 because the latter inhibits replication of both T-tropic and M-tropic isolates and does not compete with SDF-1α and 12G5 binding to CXCR4.