A Peptide Derived from Bee Venom-Secreted Phospholipase A₂Inhibits Replication of T-Cell Tropic HIV-1 Strains via Interaction with the CXCR4 Chemokine Receptor

Abstract

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.

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“…These substances are able to compete with the glycoprotein (gp120) from the viral envelope to bind with the receptor (58)(59). Furthermore, various low-molecular-weight compounds that bind to CXCR4 and inhibit HIV-1 replication have been identified (40). The ability of peptides and small molecules to block the entry of HIV through binding with CXCR4 has already been described (60-62)…”

“…The p3bv peptide prevents HIV-1 from binding to the T cells, since it binds to the CXCR4 receptor (40). Therefore, the viral particles are unable to bind to cells and after a certain period of time they become unviable since they are unable to multiply.…”

“…Recently published studies report the existence of snake venom fractions with an antiviral effect; however, few studies have been conducted to evaluate Brazilian snake venoms (39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49).…”

Honeybee venom possesses anticancer and antiviral effects by differential inhibition of HPV E6 and E7 expression on cervical cancer cell line

“…Many viruses, including hepatitis B and C, rely on the same type of protective envelope and would be vulnerable to melittin-guided BV therapy. Secreted phospholipases A2 from BV have potent anti-HIV activities (19). A nanoscale delivery vehicle for cytolytic peptides was demonstrated by incorporating the non-specific amphipathic cytolytic peptide melittin into the outer lipid monolayer of a perfluorocarbon nanoparticle (20).…”

Expression of secreted phospholipase A2-Group IIA correlates with prognosis of gastric adenocarcinoma

“…Arachidonic acid levels are known to be increased in cancer tissues (31), and arachidonic acid is the raw material for the synthesis of inflammatory mediators, including prostaglandins and leukotrienes (32). These inflammatory mediators promote tumor formation, and sPLA2-II additionally stimulates the secretion of stromal cell growth factors and cytokines, which induce cell proliferation (33). It is possible that sPLA2-II produced by gastric cancer cells may also increase the arachidonic acid levels in tumor tissues, therefore enhancing the secretion of growth factors and cytokines, and thereby promoting cancer growth.…”