Significance in replication of the terminal nucleotides of the Flavivirus genome

被引:68
作者
Khromykh, AA
Kondratieva, N
Sgro, JY
Palmenberg, A
Westaway, EG [1 ]
机构
[1] Royal Childrens Hosp, Sir Albert Sakzewski Virus Res Ctr, Brisbane, Qld 4029, Australia
[2] Univ Queensland, Clin Med Virol Ctr, Brisbane, Qld, Australia
[3] Univ Wisconsin, Madison, WI 53706 USA
关键词
D O I
10.1128/JVI.77.19.10623-10629.2003
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:10623 / 10629
页数:7
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