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Viruses 2015, 7(8), 4640-4656; doi:10.3390/v7082837

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

1
Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch at Galveston, Galveston, TX 77555-0647, USA
2
Department of Microbiology and Immunology, Georgetown University School of Medicine, Washington, DC 20057, USA
*
Author to whom correspondence should be addressed.
Academic Editor: David D. Boehr
Received: 30 June 2015 / Revised: 30 July 2015 / Accepted: 4 August 2015 / Published: 13 August 2015
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Abstract

Genome replication in flavivirus requires (—) strand RNA synthesis, (+) strand RNA synthesis, and 5’-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 5’-RNA capping and methylation. View Full-Text
Keywords: viral replication complex; flavivirus; RNA-dependent RNA polymerase; RNA synthesis; 5’-RNA capping; NS5; NS3 viral replication complex; flavivirus; RNA-dependent RNA polymerase; RNA synthesis; 5’-RNA capping; NS5; NS3
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Klema, V.J.; Padmanabhan, R.; Choi, K.H. Flaviviral Replication Complex: Coordination between RNA Synthesis and 5’-RNA Capping. Viruses 2015, 7, 4640-4656.

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