Inhibition of virus-induced cell fusion by apolipoprotein A-I and its amphipathic peptide analogs.

Academic Article

Abstract

  • Apolipoprotein A-I (apoA-I), the major protein component of serum high-density lipoproteins (HDL), was found to inhibit herpes simplex virus (HSV)-induced cell fusion at physiological (approximately 1 microM) concentrations, whereas HDL did not exert any inhibitory effect. Lipid-associating, synthetic amphipathic peptides corresponding to residues 1-33 (apoA-I[1-33]) or residues 66-120 (apoA-I[66-120]) of apoA-I, also inhibited HSV-induced cell fusion, whereas a peptide corresponding to residues 8-33 of apoA-I (apoA-I[8-33]), which fails to associate with lipids, did not exert any inhibitory effect. These results suggest that lipid binding may be a prerequisite for peptide-mediated fusion inhibition. Consistent with this idea, a series of lipid-binding 22-amino-acid-residue-long synthetic amphipathic peptides that correspond to the amphipathic helical domains of apoA-I (A-I consensus series), or 18-residue-long model amphipathic peptides (18A series), were found to exert variable levels of fusion-inhibitory activity. The extent of fusion-inhibitory activity did not correlate with hydrophobic moment, hydrophobicity of the nonpolar face, helix-forming ability, or lipid affinity of the different peptides. Peptides in which the nonpolar face was not interrupted by a charged residue displayed greater fusion-inhibitory activity. Also, the presence of positively charged residues at the polar-nonpolar interface was found to correlate with higher fusion-inhibitory activity.
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    Keywords

  • Amino Acid Sequence, Animals, Apolipoprotein A-I, Apolipoproteins A, Cell Fusion, Chemical Phenomena, Chemistry, Physical, Circular Dichroism, Depression, Chemical, Lipoproteins, HDL, Membrane Lipids, Models, Molecular, Molecular Sequence Data, Peptide Fragments, Simplexvirus, Vero Cells
  • Digital Object Identifier (doi)

    Author List

  • Srinivas RV; Venkatachalapathi YV; Rui Z; Owens RJ; Gupta KB; Srinivas SK; Anantharamaiah GM; Segrest JP; Compans RW
  • Start Page

  • 224
  • End Page

  • 237
  • Volume

  • 45
  • Issue

  • 2