Identification of naturally occurring amino acid variations that affect the ability of the measles virus C protein to regulate genome replication and transcription.
The C protein of measles virus (MV C) is a basic protein of 186 amino acids (aa) that plays at least two roles in infected cells, interference with the innate immune response and modulation of viral polymerase activity. In this study, Northern blots were used to demonstrate that C proteins from three vaccine strains and three wild-type isolates of MV downregulated both mRNA transcription and genome replication in a plasmid-based mini-genome assay. The effect on transcription always paralleled the effect on replication; however, the six MV C proteins varied considerably in their ability to inhibit polymerase activity. Though the amino-terminal 45 aa of the C protein are more variable among different MV strains than the remaining 75% of the protein, the ability of the MV C proteins to inhibit polymerase activity was not regulated by substitutions in the amino terminus, but rather by the more conserved region containing aa 46-167. Naturally occurring substitutions at positions 147 and 166, but not 88 and 186, were found to regulate MV C protein activity. Deletion of the carboxyl-terminal 19 aa did not affect the polymerase-modulating activity. Though we did not find a link between the aa changes in MV C and attenuation, these data provide new information regarding the functions of this non-structural protein.
Bankamp
Bettina
B
Measles, Mumps, Rubella and Herpes Virus Team, Centers for Disease Control and Prevention, Mail-stop C-22, 1600 Clifton Road, Atlanta, GA 30333, USA.
Wilson
Jenna
J
Bellini
William J
WJ
Rota
Paul A
PA
D019943:Amino Acid Substitution; D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D014644:Genetic Variation; D008459:Measles virus / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D012324:RNA-Dependent RNA Polymerase / Q000032:analysis / Q000037:antagonists & inhibitors; D017384:Sequence Deletion; D014158:Transcription, Genetic; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics* / Q000502:physiology*; D014779:Virus Replication
D012333:RNA, Messenger; D012367:RNA, Viral; D054334:Viral Regulatory and Accessory Proteins; D012324:RNA-Dependent RNA Polymerase