Significance in replication of the terminal nucleotides of the Flavivirus genome

Khromykh, Alexander A., Kondratieva, Natasha, Sgro, Jean-Yves, Palmenberg, Ann and Westaway, Edwin G. (2003) Significance in replication of the terminal nucleotides of the Flavivirus genome. Journal of Virology, 77 19: 10623-10629. doi:10.1128/JVI.77.19.10623-10629.2003

Author Khromykh, Alexander A.
Kondratieva, Natasha
Sgro, Jean-Yves
Palmenberg, Ann
Westaway, Edwin G.
Title Significance in replication of the terminal nucleotides of the Flavivirus genome
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
Publication date 2003-10
Year available 2003
Sub-type Article (original research)
DOI 10.1128/JVI.77.19.10623-10629.2003
Open Access Status DOI
Volume 77
Issue 19
Start page 10623
End page 10629
Total pages 7
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2003
Language eng
Subject C1
730101 Infectious diseases
270303 Virology
Abstract Point mutations that resulted in a substitution of the conserved 3'-penultimate cytidine in genomic RNA or the RNA negative strand of the self-amplifying replicon of the Flavivirus Kunjin virus completely blocked in vivo replication. Similarly, substitutions of the conserved 3'-terminal uridine in the RNA negative or positive strand completely blocked replication or caused much-reduced replication, respectively. The same preference for cytidine in the 3'-terminal dinucleotide was noted in reports of the in vitro activity of the RNA-dependent RNA polymerase (RdRp) for the other genera of Flaviviridae that also employ a double-stranded RNA (dsRNA) template to initiate asymmetric semiconservative RNA positive-strand synthesis. The Kunjin virus replicon results were interpreted in the context of a proposed model for initiation of RNA synthesis based on the solved crystal structure of the RdRp of phi6 bacteriophage, which also replicates efficiently using a dsRNA template with conserved 3'-penultimate cytidines and a 3'-terminal pyrimidine. A previously untested substitution of the conserved pentanucleotide at the top of the 3'-terminal stem-loop of all Flavivirus species also blocked detectable in vivo replication of the Kunjin virus replicon RNA.
Keyword Flavivirus
Rna Replication
Rna Structure
Hepatitis-c Virus
Dependent Rna-polymerase
Viral Diarrhea Virus
5' Nontranslated Region
Protein 5b Polymerase
De-novo Initiation
Kunjin Virus
Secondary Structure
Q-Index Code C1
Institutional Status UQ

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Created: Tue, 14 Aug 2007, 19:21:53 EST