title: A single amino acid substitution in the measles virus F₂ protein reciprocally modulates membrane fusion activity in pathogenic and oncolytic strains.
abstract: Differences in fusion activity between measles virus (MV) attenuated, oncolytic strain MV(NSe) and pathogenic MV(wt323) are reflected in amino acid 94 of the fusion (F) proteins. A valine 94 in F(NSe) (naturally) or F(wt323) (introduced) correlated with enhanced cell-cell fusion activity during transient glycoprotein expression or recombinant MV infections irrespective of the strains' targeted receptors, whereas the reverse effect was found for methionine 94. Enhanced fusogenicity was determined by weaker glycoprotein interaction and correlated positively with cytotoxicity in both virus strains. Amino acid 94 of F can be used to tailor fusogenicity and cytotoxicity of recombinant MV, while the cellular receptor triggering fusion is not decisive.
authors.affiliation: Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, D-63225 Langen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Heidmeier
authors.affiliation: Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, D-63225 Langen, Germany.
authors.forename: Jan R H
authors.initials: JR
authors.lastname: Hanauer
authors.affiliation: Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, D-63225 Langen, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Friedrich
authors.affiliation: Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, D-63225 Langen, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Prüfer
authors.affiliation: Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, D-63225 Langen, Germany.
authors.forename: Irene C
authors.initials: IC
authors.lastname: Schneider
authors.affiliation: Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, D-63225 Langen, Germany.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Buchholz
authors.affiliation: Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, D-63225 Langen, Germany; German Centre for Infection Research, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, D-63225 Langen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Cichutek
authors.affiliation: Oncolytic Measles Viruses and Vaccine Vectors, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, D-63225 Langen, Germany; German Centre for Infection Research, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, D-63225 Langen, Germany. Electronic address: Michael.Muehlebach@pei.de.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Mühlebach
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002459:Cell Fusion; D002470:Cell Survival; D002522:Chlorocebus aethiops; D008459:Measles virus / Q000235:genetics* / Q000502:physiology*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000235:genetics* / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D050505:Mutant Proteins; D014760:Viral Fusion Proteins
keywords: Fusion protein; Measles virus; Membrane fusion; Receptor usage