Membrane fusion-inhibiting peptides do not inhibit influenza virus fusion or the Ca(2+)-induced fusion of negatively charged vesicles.

Abstract

Short hydrophobic N-carbobenzoxy oligopeptides are known to inhibit the infectivity of several enveloped viruses. Recently, it was shown that they inhibited the fusion of Sendai virus with N-methyl-dioleoylphosphatidylethanolamine (N-methyl-DOPE) liposomes as well as the low pH-induced fusion of these liposomes with each other (Kelsey, D.R., Flanagan, T. D., Young, J. E., and Yeagle, P. L. (1990) J. Biol. Chem. 265, 12178-12183). Therefore it was concluded that the peptides inhibit membrane fusion, an important step in viral infectivity. Here, it is shown that this peptide and a series of similar peptides did not inhibit influenza virus fusion with N-methyl-DOPE or other liposomes. In fact, some peptides enhanced the overall rate of fusion of influenza virus with N-methyl-DOPE liposomes. In our hands, the peptides did not inhibit influenza infectivity in Madin-Darby canine kidney cells or influenza-induced hemolysis either. They also did not inhibit the Ca(2+)-induced fusion between cardiolipin or phosphatidylserine liposomes. However, the inhibitory effect of one of the peptides on the fusion of Sendai virus with N-methyl-DOPE liposomes and on N-methyl-DOPE liposome-liposome fusion could be reproduced. These data indicate that the peptides do not, as had been suggested (Yeagle, P.L., Young, J.E., Hui, S.W., and Epand, R. M. (1992) Biochemistry 31, 3177-3183), act by preventing the formation of lipid structures with small radii of curvature, such as the inverted phase intermediates that are thought to be involved in N-methyl-DOPE fusion. The results also suggest that the mechanism of inhibition of Sendai virus infection and N-methyl-DOPE fusion by the peptides may be different after all.