A single point mutation controls the cholesterol dependence of Semliki Forest virus entry and exit

Malini Vashishtha, Thomas Phalen, Marianne T. Marquardt, Jae S. Ryu, Alice C. Ng, Margaret Kielian

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114 Scopus citations


Membrane fusion and budding are key steps in the life cycle of all enveloped viruses. Semliki Forest virus (SFV) is an enveloped alphavirus that requires cellular membrane cholesterol for both membrane fusion and efficient exit of progeny virus from infected cells. We selected an SFV mutant, srf-3, that was strikingly independent of cholesterol for growth. This phenotype was conferred by a single amino acid change in the E1 spike protein subunit, proline 226 to serine, that increased the cholesterol independence of both srf-3 fusion and exit. The srf-3 mutant emphasizes the relationship between the role of cholesterol in membrane fusion and virus exit, and most significantly, identifies a novel spike protein region involved in the virus cholesterol requirement.

Original languageEnglish (US)
Pages (from-to)91-99
Number of pages9
JournalJournal of Cell Biology
Issue number1
Publication statusPublished - Jan 12 1998


ASJC Scopus subject areas

  • Cell Biology

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