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 A2 (sPLA2) from bee and snake venoms have potent anti-human immunodeficiency virus (HIV) activity. 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 (ID(50) = 2 microM) 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)-1alpha, 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-1alpha and 12G5 binding to CXCR4.
Fenard
D
D
Laboratoire de Virologie, Institut National de la Sante et de la Recherche Medicale U526, Faculté de Médecine, Nice, France.
Lambeau
G
G
Maurin
T
T
Lefebvre
J C
JC
Doglio
A
A
D000595:Amino Acid Sequence; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D001514:Bee Venoms / Q000201:enzymology*; D002450:Cell Communication / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D019718:Receptors, CXCR4 / Q000187:drug effects / Q000378:metabolism*; D013601:T-Lymphocytes / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D001514:Bee Venoms; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D010455:Peptides; D019718:Receptors, CXCR4; D010741:Phospholipases A; D054467:Phospholipases A2