Differential cholesterol binding by class II fusion proteins determines membrane fusion properties

M. Umashankar, Claudia Sánchez-San Martín, Maofu Liao, Brigid Reilly, Alice Guo, Gwen Taylor, Margaret Kielian

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


The class II fusion proteins of the alphaviruses and flaviviruses mediate virus infection by driving the fusion of the virus membrane with that of the cell. These fusion proteins are triggered by low pH, and their structures are strikingly similar in both the prefusion dimer and the postfusion homotrimer conformations. Here we have compared cholesterol interactions during membrane fusion by these two groups of viruses. Using cholesteroldepleted insect cells, we showed that fusion and infection by the alphaviruses Semliki Forest virus (SFV) and Sindbis virus were strongly promoted by cholesterol, with similar sterol dependence in laboratory and field isolates and in viruses passaged in tissue culture. The E1 fusion protein from SFV bound cholesterol, as detected by labeling with photocholesterol and by cholesterol extraction studies. In contrast, fusion and infection by numerous strains of the flavivirus dengue virus (DV) and by yellow fever virus 17D were cholesterol independent, and the DV fusion protein did not show significant cholesterol binding. SFV E1 is the first virus fusion protein demonstrated to directly bind cholesterol. Taken together, our results reveal important functional differences conferred by the cholesterol-binding properties of class II fusion proteins.

Original languageEnglish (US)
Pages (from-to)9245-9253
Number of pages9
JournalJournal of virology
Issue number18
StatePublished - Sep 2008

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology


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