Flaviviral Replication Complex: Coordination between RNA Synthesis and 5'-RNA Capping

Viruses. 2015 Aug 13;7(8):4640-56. doi: 10.3390/v7082837.


Genome replication in flavivirus requires (-) strand RNA synthesis, (+) strand RNA synthesis, and 51-RNA capping and methylation. To carry out viral genome replication, flavivirus assembles a replication complex, consisting of both viral and host proteins, on the cytoplasmic side of the endoplasmic reticulum (ER) membrane. Two major components of the replication complex are the viral non-structural (NS) proteins NS3 and NS5. Together they possess all the enzymatic activities required for genome replication, yet how these activities are coordinated during genome replication is not clear. We provide an overview of the flaviviral genome replication process, the membrane-bound replication complex, and recent crystal structures of full-length NS5. We propose a model of how NS3 and NS5 coordinate their activities in the individual steps of (-) RNA synthesis, (+) RNA synthesis, and 51-RNA capping and methylation.

Keywords: 51-RNA capping; NS3; NS5; RNA synthesis; RNA-dependent RNA polymerase; flavivirus; viral replication complex.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Flavivirus / genetics
  • Flavivirus / physiology*
  • Gene Expression Regulation, Viral
  • Humans
  • RNA Caps / biosynthesis*
  • RNA Helicases / metabolism
  • RNA, Viral / biosynthesis*
  • Serine Endopeptidases / metabolism
  • Viral Nonstructural Proteins / metabolism*
  • Virus Replication*


  • NS3 protein, flavivirus
  • NS5 protein, flavivirus
  • RNA Caps
  • RNA, Viral
  • Viral Nonstructural Proteins
  • Serine Endopeptidases
  • RNA Helicases