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Journal of Virology, November 2008, p. 11437-11445, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.00779-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Measles Virus Fusion Protein Transmembrane Region Modulates Availability of an Active Glycoprotein Complex and Fusion Efficiency{triangledown}

Michael D. Mühlebach,1,2 Vincent H. J. Leonard,1 and Roberto Cattaneo1*

Department of Molecular Medicine and Virology and Gene Therapy Track, Mayo Graduate School, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905,1 Division of Medical Biotechnology, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, D-63225 Langen, Germany2

Received 10 April 2008/ Accepted 5 September 2008

The glycoprotein complex of paramyxoviruses mediates receptor binding and membrane fusion. In particular, the measles virus (MV) fusion (F) protein executes membrane fusion, after receptor binding by the hemagglutinin (H) protein. Structures and single amino acids influencing fusion function have been identified in the F-protein ectodomain and cytoplasmic tail, but not in its transmembrane (TM) region. Since this region influences function of the envelope proteins of other viruses, we examined its role in the MV F protein. Alanine-scanning mutagenesis revealed that an F protein with a single mutation of a central TM region leucine (L507A) was more fusogenic than the unmodified F protein while retaining similar kinetics of proteolytic processing. In contrast, substitution of residues located near the edges of the lipid bilayer reduced fusion activity. This was true not only when the mutated F proteins were coexpressed with H but also in the context of infections with recombinant viruses. Analysis of the H-F complexes with reduced fusion activities revealed that more precursor (F0) than activated (F1+2) protein coprecipitated with H. In contrast, in complexes with enhanced fusion activity, including H-FL507A, the F0/F1+2 ratio shifted toward F1+2. Thus, fusion activity correlated with an active F-H protein complex, and the MV F protein TM region modulated availability of this complex.

* Corresponding author. Mailing address: Mayo Clinic, Department of Molecular Medicine, 200 First Street SW, Rochester, MN 55905. Phone: (507) 538-1188. Fax: (507) 266-2122. E-mail: Cattaneo.Roberto{at}mayo.edu

{triangledown} Published ahead of print on 10 September 2008.

Journal of Virology, November 2008, p. 11437-11445, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.00779-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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