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

We have previously shown that secreted phospholipases A(2) (sPLA(2)) from bee and snake venoms have potent anti-human immunodeficiency virus (HIV activity (Fenard et al., 1999). These sPLA(2)s block HIV-1 entry into host cells through a mechanism linked to sPLA(2) binding to cells. In this study, 12 synthetic peptides derived from bee venom sPLA(2) (bvPLA(2)) have been tested for inhibition of HIV-1 infection. The p3bv peptide (amino acids 21 to 35 of bvPLA(2)) was found to inhibit the replication of T-lymphotropic (T-tropic) HIV-1 isolates (ID50 = 2 muM) 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 alpha, 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 by PLA(2) because the latter inhibits replication of both T-tropic and M-tropic isolates and does not compete with SDF-1 alpha and 12G5 binding to CXCR4.