Reversible acid-induced inactivation of the membrane fusion protein of Semliki Forest virus

BL Waarts, JM Smit, OJC Aneke, GM McInerney, P Liljestrom, R Bittman, J Wilschut*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    11 Citations (Scopus)

    Abstract

    Previously, it has been shown that the exposure of Semliki Forest virus (SFV) to a mildly acidic environment induces a rapid and complete loss of the ability of the virus to bind and fuse to target membranes added subsequently. In the present study, incubation of SFV at low pH followed by a specific reneutralization step resulted in a partial reversion of this loss of viral fusion capacity, as assessed in a liposomal model system. Also, the ability of the viral El fusion protein to undergo liposome-stimulated trimerization was restored. Furthermore, acid-treated and neutralized SFV largely retained infectivity. Exposure of SFV to low pH induced dissociation of the E1/E2 heterodimer, which was not reversed upon neutralization. It is concluded that the SFV El fusion protein, after acid-induced dissociation from E2, rapidly adopts an intermediate, nontrimeric conformation in which it is no longer able to interact with target membrane lipids. Neutralization restores the ability of El to interact with membranes. This interaction, however, remains strictly dependent on low pH.

    Original languageEnglish
    Pages (from-to)7942-7948
    Number of pages7
    JournalJournal of Virology
    Volume79
    Issue number12
    DOIs
    Publication statusPublished - Jun-2005

    Keywords

    • CHOLESTEROL-CONTAINING LIPOSOMES
    • PH-DEPENDENT FUSION
    • ENVELOPE GLYCOPROTEIN
    • TARGET-MEMBRANE
    • SINDBIS-VIRUS
    • MODEL SYSTEM
    • SPHINGOLIPIDS
    • PEPTIDE
    • ENTRY
    • HEMAGGLUTININ

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