PMID: 9557718Apr 29, 1998Paper

fus-1, a pH shift mutant of Semliki Forest virus, acts by altering spike subunit interactions via a mutation in the E2 subunit

Journal of Virology
S Glomb-Reinmund, M Kielian

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 of fus-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 and fus-1 E2. Sequence analysis demonstrated that the fus-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 ammoniu...Continue Reading

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Citations

Jun 17, 2011·Virology Journal·Joseph P KononchikDennis T Brown
Apr 29, 2016·Journal of Virology·Mathieu DubéMargaret Kielian
Apr 29, 2015·Viruses·Yaw Shin OoiMargaret Kielian
Dec 21, 2002·The Journal of Biological Chemistry·Lena HammarR Holland Cheng
Mar 26, 2010·Viruses·Margaret KielianMaofu Liao
Feb 13, 2016·Journal of Virology·Katie M Stiles, Margaret Kielian
Dec 5, 2014·PLoS Pathogens·Mathieu DubéMargaret Kielian
May 2, 2019·Frontiers in Microbiology·Mariano Prado AcostaMaria Guadalupe Martinez
Feb 14, 2003·Journal of Virology·Xinyong ZhangMargaret Kielian
Aug 10, 2000·Journal of Virology·Y E Lu, M Kielian
May 13, 2011·Virology·Joseph P KononchikDennis T Brown

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