A Highly Structured, Nuclease-Resistant, Noncoding RNA Produced by Flaviviruses Is Required for Pathogenicity

被引:379
作者
Pijlman, Gorben P. [1 ]
Funk, Anneke [1 ]
Kondratieva, Natasha [1 ]
Leung, Jason [1 ]
Torres, Shessy [1 ]
van der Aa, Lieke [1 ]
Liu, Wen Jun [1 ]
Palmenberg, Ann C. [2 ]
Shi, Pei-Yong [3 ,4 ,5 ]
Hall, Roy A. [1 ]
Khromykh, Alexander A. [1 ]
机构
[1] Univ Queensland, Sch Mol & Microbial Sci, Brisbane, Qld 4072, Australia
[2] Univ Wisconsin, Inst Mol Virol, Madison, WI 53706 USA
[3] SUNY Albany, New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA
[4] SUNY Albany, Dept Biomed Sci, Albany, NY 12201 USA
[5] Novartis Inst Trop Dis, Singapore 138670, Singapore
基金
英国医学研究理事会;
关键词
D O I
10.1016/j.chom.2008.10.007
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Viral noncoding RNAs have been shown to play an important role in virus-host interplay to facilitate virus replication. We report that members of the genus Flavivirus, a large group of medically important encephalitic RNA viruses, produce a unique and highly structured noncoding RNA of 0.3-0.5 kb derived from the 3' untranslated region of the viral genome. Using West Nile virus as a model, we show that this subgenomic RNA is a product of incomplete degradation of viral genomic RNA by cellular ribonucleases. Highly conserved RNA structures located at the beginning of the 3' untranslated region render this RNA resistant to nucleases, and the resulting subgenomic RNA product is essential for virus-induced cytopathicity and pathogenicity. Thus, flaviviruses evolved a unique strategy to generate a noncoding RNA product that allows them to kill the host more efficiently.
引用
收藏
页码:579 / 591
页数:13
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