Domain III from class II fusion proteins functions as a dominant-negative inhibitor of virus membrane fusion

Maofu Liao, Margaret Kielian

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Alphaviruses and flaviviruses infect cells through low pH-dependent membrane fusion reactions mediated by their structurally similar viral fusion proteins. During fusion, these class II viral fusion proteins trimerize and refold to form hairpin-like structures, with the domain III and stem regions folded back toward the target membrane-inserted fusion peptides. We demonstrate that exogenous domain III can function as a dominant-negative inhibitor of alphavirus and flavivirus membrane fusion and infection. Domain III binds stably to the fusion protein, thus preventing the foldback reaction and blocking the lipid mixing step of fusion. Our data reveal the existence of a relatively long-lived core trimer intermediate with which domain III interacts to initiate membrane fusion. These novel inhibitors of the class II fusion proteins show crossinhibition within the virus genus and suggest that the domain III-core trimer interaction can serve as a new target for the development of antiviral reagents.

Original languageEnglish (US)
Pages (from-to)111-120
Number of pages10
JournalJournal of Cell Biology
Volume171
Issue number1
DOIs
StatePublished - Oct 2005

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Virus Internalization
Membrane Fusion
Viral Fusion Proteins
Alphavirus
Flavivirus
Proteins
Protein Refolding
Antiviral Agents
Viruses
Lipids
Peptides
Infection
2',5'-oligoisoadenosine

ASJC Scopus subject areas

  • Cell Biology

Cite this

Domain III from class II fusion proteins functions as a dominant-negative inhibitor of virus membrane fusion. / Liao, Maofu; Kielian, Margaret.

In: Journal of Cell Biology, Vol. 171, No. 1, 10.2005, p. 111-120.

Research output: Contribution to journalArticle

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