Prefusion rearrangements resulting in fusion peptide exposure in Semliki Forest virus

Lena Hammar, Sevak Markarian, Lars Haag, Hilkka Lankinen, Aimo Salmi, R. Holland Cheng

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Semliki Forest virus (SFV), like many enveloped viruses, takes advantage of the low pH in the endosome to convert into a fusion-competent configuration and complete infection by fusion with the endosomal membrane. Unlike influenza virus, carrying an N-terminal fusion peptide, SFV represents a less-well understood fusion principle involving an endosequence fusion peptide. To explore the series of events leading to a fusogenic configuration of the SFV, we exposed the virus to successive acidification, mimicking endosomal conditions, and followed structural rearrangements at probed sensor surfaces. Thus revealed, the initial phase involves a transient appearance of a non-linear neutralizing antibody epitope in the fusion protein, E1. Concurrent with the disappearance of this epitope, a set of masked sequences in proteins E1 and E2 became exposed. When pH reached 6.0-5.9 the virion transformed into a configuration of enlarged diameter with the fusion peptide optimally exposed. Simultaneously, a partly hidden sequence close to the receptor binding site in E2 became fully uncovered. At this presumably fusogenic stage, maximally 80 fusion peptide-identifying antibody Fab fragments could be bound per virion, i.e. one ligand per three copies of the fusion protein. The phenomena observed are discussed in terms of alphavirus structure and reported functional domains.

Original languageEnglish (US)
Pages (from-to)7189-7198
Number of pages10
JournalJournal of Biological Chemistry
Volume278
Issue number9
DOIs
StatePublished - Feb 28 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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    Hammar, L., Markarian, S., Haag, L., Lankinen, H., Salmi, A., & Holland Cheng, R. (2003). Prefusion rearrangements resulting in fusion peptide exposure in Semliki Forest virus. Journal of Biological Chemistry, 278(9), 7189-7198. https://doi.org/10.1074/jbc.M206015200