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Journal of Virology, May 2002, p. 5051-5061, Vol. 76, No. 10
0022-538X/02/$04.00+0 DOI: 10.1128/JVI.76.10.5051-5061.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Strength of Envelope Protein Interaction Modulates Cytopathicity of Measles Virus
Richard K. Plemper,1* Anthea L. Hammond,1 Denis Gerlier,2 Adele K. Fielding,1 and Roberto Cattaneo1
Molecular Medicine Program, Mayo Foundation, Rochester, Minnesota 55905,1
Immunite et Infections Virales, CNRS-UCBL UMR5537, IFR Laennec, 69372 Lyon Cedex 08, France2
Received 11 October 2001/
Accepted 8 February 2002
To understand the molecular determinants of measles virus (MV) cytopathicity, we have characterized mutant viruses exhibiting a more-extensive cell-to-cell fusion while maintaining efficient replication to high titers. A virus which is modified by the addition of an 8-amino-acid Flag epitope tag at the cytoplasmic tail of its H (for MV hemagglutinin) envelope glycoprotein replicates efficiently, has an increased cytopathicity, possesses a greater infectivity per particle, and has an altered protein composition compared with that of unmodified MV. The mutant phenotype is not specifically linked to the epitope sequence, since an alternatively added HA (for influenza virus-derived hemagglutinin) epitope tag caused similar effects. We demonstrate that both epitope tags weaken the interaction between the H and fusion (F) glycoproteins in virus-infected cells. This reduction in strength of H/F interaction is independent of the presence of the viral matrix (M) protein. Viruses with this less stable complex are more sensitive to neutralization by a soluble octameric form of the CD46 receptor, consistent with their increased fusogenicity. Similar analyses of glycoproteins derived from MV strains with reduced cytopathicities confirm that the strength of H and F glycoprotein interaction is a modulator of viral fusogenicity.
* Corresponding author. Present address: Department of Microbiology & Immunology, Emory University, 3001 Rollins Research Center, 1510 Clifton Rd., Atlanta, GA 30322. Phone: (404) 727-3228. Fax: (404) 727-8250. E-mail: rplempe{at}emory.edu.
Journal of Virology, May 2002, p. 5051-5061, Vol. 76, No. 10
0022-538X/02/$04.00+0 DOI: 10.1128/JVI.76.10.5051-5061.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
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Copyright © 2002 by the American Society for Microbiology. All rights reserved.