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Virus-Cell Interactions

fus-1, a pH Shift Mutant of Semliki Forest Virus, Acts by Altering Spike Subunit Interactions via a Mutation in the E2 Subunit

Sallie Glomb-Reinmund, Margaret Kielian
Sallie Glomb-Reinmund
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461
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Margaret Kielian
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461
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DOI: 10.1128/JVI.72.5.4281-4287.1998
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ABSTRACT

Semliki Forest virus (SFV), an enveloped alphavirus, is a well-characterized paradigm for viruses that infect cells via endocytic uptake and low-pH-triggered fusion. The SFV spike protein is composed of a dimer of E1 and E2 transmembrane subunits, which dissociate upon exposure to low pH, liberating E2 and the fusogenic E1 subunit to undergo independent conformational changes. SFV fusion and infection are blocked by agents such as ammonium chloride, which act by raising the pH in the endosome and inhibiting the low-pH-induced conformational changes in the SFV spike protein. We have previously isolated an SFV mutant, fus-1, that requires more acidic pH to trigger its fusion activity and is therefore more sensitive to inhibition by ammonium chloride. The acid shift in the fusion activity offus-1 was here shown to be due to a more acidic pH threshold for the initial dissociation of the fus-1 spike dimer, thereby resulting in a more acidic pH requirement for the subsequent conformational changes in both fus-1 E1 andfus-1 E2. Sequence analysis demonstrated that thefus-1 phenotype was due to a mutation in the E2 spike subunit, threonine 12 to isoleucine. fus-1 revertants that have regained the parental fusion phenotype and ammonium chloride sensitivity were shown to have also regained E2 threonine 12. Our results identify a region of the SFV E2 spike protein subunit that regulates the pH dependence of E1-catalyzed fusion by controlling the dissociation of the E1/E2 dimer.

  • Copyright © 1998 American Society for Microbiology
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fus-1, a pH Shift Mutant of Semliki Forest Virus, Acts by Altering Spike Subunit Interactions via a Mutation in the E2 Subunit
Sallie Glomb-Reinmund, Margaret Kielian
Journal of Virology May 1998, 72 (5) 4281-4287; DOI: 10.1128/JVI.72.5.4281-4287.1998

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fus-1, a pH Shift Mutant of Semliki Forest Virus, Acts by Altering Spike Subunit Interactions via a Mutation in the E2 Subunit
Sallie Glomb-Reinmund, Margaret Kielian
Journal of Virology May 1998, 72 (5) 4281-4287; DOI: 10.1128/JVI.72.5.4281-4287.1998
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KEYWORDS

mutation
Semliki Forest virus
Viral Envelope Proteins

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