Vol. 60, Issue 2, 341-347, August 2001

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

David Fenard, Gerard Lambeau, Thomas Maurin, Jean-Claude Lefebvre, and Alain Doglio

Laboratoire de Virologie, Institut National de la Sante et de la Recherche Medicale U526, Faculté de Médecine, Nice, France (D.F., T.M., J.C.L., A.D.); and Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique UPR411, Valbonne, France (G.L.)

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)-1, 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-1 and 12G5 binding to CXCR4.