Inhibition of virus-induced cell fusion by apolipoprotein A-I and its amphipathic peptide analogs.
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.
Srinivas
R V
RV
Department of Microbiology, University of Alabama, Birmingham 35294.
Venkatachalapathi
Y V
YV
Rui
Z
Z
Owens
R J
RJ
Gupta
K B
KB
Srinivas
S K
SK
Anantharamaiah
G M
GM
Segrest
J P
JP
Compans
R W
RW
D000595:Amino Acid Sequence; D000818:Animals; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000494:pharmacology*; D002459:Cell Fusion / Q000187:drug effects*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002942:Circular Dichroism; D003864:Depression, Chemical; D008075:Lipoproteins, HDL / Q000494:pharmacology; D008563:Membrane Lipids / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D018139:Simplexvirus / Q000502:physiology*; D014709:Vero Cells
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D008075:Lipoproteins, HDL; D008563:Membrane Lipids; D010446:Peptide Fragments