Strength of envelope protein interaction modulates cytopathicity of measles virus.
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.
Plemper
Richard K
RK
Molecular Medicine Program, Mayo Foundation, Rochester, Minnesota 55905, USA. rplempe@emory.edu
Hammond
Anthea L
AL
Gerlier
Denis
D
Fielding
Adele K
AK
Cattaneo
Roberto
R
D000818:Animals; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral; D000939:Epitopes / Q000235:genetics; D015726:Giant Cells; D006023:Glycoproteins / Q000378:metabolism*; D006367:HeLa Cells; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008459:Measles virus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D009842:Oligopeptides; D010455:Peptides / Q000235:genetics; D011995:Recombination, Genetic; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism*
D000939:Epitopes; D006023:Glycoproteins; D006389:Hemagglutinins, Viral; D009842:Oligopeptides; D010455:Peptides; D014759:Viral Envelope Proteins; C032397:hemagglutinin protein G, measles virus; C085706:FLAG peptide