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

• Published in: Molecular pharmacology 2001-08, Vol.60 (2), p.341-347
• Main Authors: Fenard, D, Lambeau, G, Maurin, T, Lefebvre, J C, Doglio, A
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Anti-HIV Agents - pharmacology; Antibodies, Monoclonal - immunology; Bee Venoms - enzymology; Cell Communication - drug effects; Chemokine CXCL12; Chemokines, CXC - metabolism; HIV-1 - drug effects; HIV-1 - physiology; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; Peptides - chemical synthesis; Peptides - chemistry; Peptides - pharmacology; Phospholipases A - pharmacology; Phospholipases A2; Receptors, CXCR4 - drug effects; Receptors, CXCR4 - metabolism; T-Lymphocytes - virology; Virus Replication - drug effects
• ISSN: 0026-895X; 1521-0111
• DOI: 10.1124/mol.60.2.341

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 (ID 50 = 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 bvPLA 2 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.