Strength of envelope protein interaction modulates cytopathicity of measles virus

Richard K. Plemper, Anthea L. Hammond, Denis Gerlier, Adele K. Fielding, Roberto Cattaneo

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5051-5061
Number of pages11
JournalJournal of Virology
Volume76
Issue number10
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Measles virus
glycoproteins
Epitopes
Glycoproteins
Viral Matrix Proteins
Viruses
viruses
Hemagglutinins
hemagglutinins
Proteins
proteins
mutants
cell fusion
Cell Fusion
protein composition
Orthomyxoviridae
neutralization
epitopes
tail
pathogenicity

ASJC Scopus subject areas

  • Immunology

Cite this

Strength of envelope protein interaction modulates cytopathicity of measles virus. / Plemper, Richard K.; Hammond, Anthea L.; Gerlier, Denis; Fielding, Adele K.; Cattaneo, Roberto.

In: Journal of Virology, Vol. 76, No. 10, 2002, p. 5051-5061.

Research output: Contribution to journalArticle

Plemper, Richard K. ; Hammond, Anthea L. ; Gerlier, Denis ; Fielding, Adele K. ; Cattaneo, Roberto. / Strength of envelope protein interaction modulates cytopathicity of measles virus. In: Journal of Virology. 2002 ; Vol. 76, No. 10. pp. 5051-5061.
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