Dynamics of viral RNA synthesis during measles virus infection.
We propose a reference model of the kinetics of a viral RNA-dependent RNA polymerase (vRdRp) activities and its regulation during infection of eucaryotic cells. After measles virus infects a cell, mRNAs from all genes immediately start to accumulate linearly over the first 5 to 6 h and then exponentially until approximately 24 h. The change from a linear to an exponential accumulation correlates with de novo synthesis of vRdRp from the incoming template. Expression of the virus nucleoprotein (N) prior to infection shifts the balance in favor of replication. Conversely, inhibition of protein synthesis by cycloheximide favors the latter. The in vivo elongation speed of the viral polymerase is approximately 3 nucleotides/s. A similar profile with fivefold-slower kinetics can be obtained using a recombinant virus expressing a structurally altered polymerase. Finally, virions contain only encapsidated genomic, antigenomic, and 5'-end abortive replication fragment RNAs.
Plumet
Sébastien
S
Immunité & Infections Virales, CNRS-University of Lyon 1 UMR 5537, IFR Laennec, 69372 Lyon Cedex 08, France.
Duprex
W Paul
WP
Gerlier
Denis
D
D002460:Cell Line; D004795:Enzyme Stability; D016679:Genome, Viral; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008457:Measles / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D008459:Measles virus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D008954:Models, Biological; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000096:biosynthesis* / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins; C058314:nucleoprotein, Measles virus; D012324:RNA-Dependent RNA Polymerase