. Dynamics of viral RNA synthesis during measles virus infection.
Abstract
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.
Keywords
Enzyme Stability
Genome
Viral
Hela Cells
Humans
Kinetics
Measles/etiology/genetics/metabolism/*virology
Measles virus/genetics/*metabolism/pathogenicity
Models
Biological
Nucleoproteins/genetics/metabolism
RNA Replicase/metabolism
RNA
Messenger/genetics/metabolism
Viral/*biosynthesis/genetics
Transcription
Genetic
Viral Proteins/genetics/metabolism