Oligopeptides that specifically inhibit membrane fusion by paramyxoviruses: Studies on the site of action

Christopher D. Richardson, Purnell W. Choppin

Research output: Contribution to journalArticlepeer-review

129 Citations (Scopus)

Abstract

Previous studies from this laboratory showed that oligopeptides with amino acid sequences similar to the sequence of the N-terminal region of the F1 polypeptide of paramyxoviruses inhibited the membrane fusing activity of the F protein, and thereby inhibited virus infectivity at the level of penetration and virus-induced cell fusion and hemolysis. The site of action of these oligopeptide inhibitors has been investigated. Radioactively labeled oligopeptides were found to bind to cells, but not to virus. Pretreatment of cells, but not virus, at 4° with oligopeptides inhibited the initiation of infection and hemolysis induced by measles virus. The binding of the oligopeptides to cells was reversible at 25 or 37°. Oligopeptides were synthesized with a chloromethylketone group to enable them to bind irreversibly, or with an azido group to permit them to be cross-linked in situ by photoactivation. The results with these derivatized oligopeptides, which retained their inhibitory activity, confirmed that they bind to, and express their inhibitory activity on, cells and not virus. The results suggest that the oligopeptides react with receptor sites on the cell membrane and inhibit membrane-fusing activity by competing with the F1 polypeptide for such sites. A Scatchard analysis of the binding of an oligopeptide to CV-1 cells revealed that it bound with a dissociation constant of 1.2 × 10-7 M and that there were ∼3.0 × 106 binding sites per cell.

Original languageEnglish
Pages (from-to)518-532
Number of pages15
JournalVirology
Volume131
Issue number2
DOIs
Publication statusPublished - Dec 1983
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported by research Grants AI-05600 from the National Institute of Allergy and Infectious Diseases, PCM80-13464 from the National Science Foundation, and RG-1216-B-3 from the National Multiple Sclerosis Society .

ASJC Scopus Subject Areas

  • Virology

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