Small Noncoding RNA Modulates Japanese Encephalitis Virus Replication and Translation in Trans

Overview

Journal Virol J

Publisher Biomed Central

Specialty Microbiology

Date 2011 Nov 2

PMID 22040380

Citations 28

Authors

Yi-Hsin Fan

Muthukumar Nadar

Chiu-Chin Chen

Chia-Chen Weng

Yun-Tong Lin

Ruey-Yi Chang

Affiliations

Soon will be listed here.

Abstract

Background: Sequence and structural elements in the 3'-untranslated region (UTR) of Japanese encephalitis virus (JEV) are known to regulate translation and replication. We previously reported an abundant accumulation of small subgenomic flaviviral RNA (sfRNA) which is collinear with the highly conserved regions of the 3'-UTR in JEV-infected cells. However, function of the sfRNA in JEV life cycle remains unknown.

Results: Northern blot and real-time RT-PCR analyses indicated that the sfRNA becomes apparent at the time point at which minus-strand RNA (antigenome) reaches a plateau suggesting a role for sfRNA in the regulation of antigenome synthesis. Transfection of minus-sense sfRNA into JEV-infected cells, in order to counter the effects of plus-sense sfRNA, resulted in higher levels of antigenome suggesting that the presence of the sfRNA inhibits antigenome synthesis. Trans-acting effect of sfRNA on JEV translation was studied using a reporter mRNA containing the luciferase gene fused to partial coding regions of JEV and flanked by the respective JEV UTRs. In vivo and in vitro translation revealed that sfRNA inhibited JEV translation.

Conclusions: Our results indicate that sfRNA modulates viral translation and replication in trans.

Citing Articles

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References

Blackwell J, Brinton M . BHK cell proteins that bind to the 3' stem-loop structure of the West Nile virus genome RNA. J Virol. 1995; 69(9):5650-8. PMC: 189422. DOI: 10.1128/JVI.69.9.5650-5658.1995. View

Blackwell J, Brinton M . Translation elongation factor-1 alpha interacts with the 3' stem-loop region of West Nile virus genomic RNA. J Virol. 1997; 71(9):6433-44. PMC: 191917. DOI: 10.1128/JVI.71.9.6433-6444.1997. View

Villordo S, Alvarez D, Gamarnik A . A balance between circular and linear forms of the dengue virus genome is crucial for viral replication. RNA. 2010; 16(12):2325-35. PMC: 2995394. DOI: 10.1261/rna.2120410. View

Filomatori C, Lodeiro M, Alvarez D, Samsa M, Pietrasanta L, Gamarnik A . A 5' RNA element promotes dengue virus RNA synthesis on a circular genome. Genes Dev. 2006; 20(16):2238-49. PMC: 1553207. DOI: 10.1101/gad.1444206. View

Chu P, WESTAWAY E . Replication strategy of Kunjin virus: evidence for recycling role of replicative form RNA as template in semiconservative and asymmetric replication. Virology. 1985; 140(1):68-79. DOI: 10.1016/0042-6822(85)90446-5. View

Uchil P, Kumar A, Satchidanandam V . Nuclear localization of flavivirus RNA synthesis in infected cells. J Virol. 2006; 80(11):5451-64. PMC: 1472159. DOI: 10.1128/JVI.01982-05. View

Pogany J, Fabian M, White K, Nagy P . A replication silencer element in a plus-strand RNA virus. EMBO J. 2003; 22(20):5602-11. PMC: 213777. DOI: 10.1093/emboj/cdg523. View

Chen L, Lin Y, Liao C, Lin C, Huang Y, Yeh C . Generation and characterization of organ-tropism mutants of Japanese encephalitis virus in vivo and in vitro. Virology. 1996; 223(1):79-88. DOI: 10.1006/viro.1996.0457. View

Pijlman G, Funk A, Kondratieva N, Leung J, Torres S, van der Aa L . A highly structured, nuclease-resistant, noncoding RNA produced by flaviviruses is required for pathogenicity. Cell Host Microbe. 2008; 4(6):579-91. DOI: 10.1016/j.chom.2008.10.007. View

10.

Frolov I, Hardy R, Rice C . Cis-acting RNA elements at the 5' end of Sindbis virus genome RNA regulate minus- and plus-strand RNA synthesis. RNA. 2001; 7(11):1638-51. PMC: 1370205. DOI: 10.1017/s135583820101010x. View

11.

Paranjape S, Harris E . Y box-binding protein-1 binds to the dengue virus 3'-untranslated region and mediates antiviral effects. J Biol Chem. 2007; 282(42):30497-508. DOI: 10.1074/jbc.M705755200. View

12.

Holden K, Harris E . Enhancement of dengue virus translation: role of the 3' untranslated region and the terminal 3' stem-loop domain. Virology. 2004; 329(1):119-33. DOI: 10.1016/j.virol.2004.08.004. View

13.

Wei Y, Qin C, Jiang T, Li X, Zhao H, Liu Z . Translational regulation by the 3' untranslated region of the dengue type 2 virus genome. Am J Trop Med Hyg. 2009; 81(5):817-24. DOI: 10.4269/ajtmh.2009.08-0595. View

14.

Tilgner M, Shi P . Structure and function of the 3' terminal six nucleotides of the west nile virus genome in viral replication. J Virol. 2004; 78(15):8159-71. PMC: 446100. DOI: 10.1128/JVI.78.15.8159-8171.2004. View

15.

Yun S, Choi Y, Song B, Lee Y . 3' cis-acting elements that contribute to the competence and efficiency of Japanese encephalitis virus genome replication: functional importance of sequence duplications, deletions, and substitutions. J Virol. 2009; 83(16):7909-30. PMC: 2715749. DOI: 10.1128/JVI.02541-08. View

16.

Alvarez D, De Lella Ezcurra A, Fucito S, Gamarnik A . Role of RNA structures present at the 3'UTR of dengue virus on translation, RNA synthesis, and viral replication. Virology. 2005; 339(2):200-12. DOI: 10.1016/j.virol.2005.06.009. View

17.

Silva P, Pereira C, Dalebout T, Spaan W, Bredenbeek P . An RNA pseudoknot is required for production of yellow fever virus subgenomic RNA by the host nuclease XRN1. J Virol. 2010; 84(21):11395-406. PMC: 2953177. DOI: 10.1128/JVI.01047-10. View

18.

Davis W, Blackwell J, Shi P, Brinton M . Interaction between the cellular protein eEF1A and the 3'-terminal stem-loop of West Nile virus genomic RNA facilitates viral minus-strand RNA synthesis. J Virol. 2007; 81(18):10172-87. PMC: 2045417. DOI: 10.1128/JVI.00531-07. View

19.

Zhang B, Dong H, Stein D, Iversen P, Shi P . West Nile virus genome cyclization and RNA replication require two pairs of long-distance RNA interactions. Virology. 2008; 373(1):1-13. DOI: 10.1016/j.virol.2008.01.016. View

20.

De Nova-Ocampo M, Villegas-Sepulveda N, Del Angel R . Translation elongation factor-1alpha, La, and PTB interact with the 3' untranslated region of dengue 4 virus RNA. Virology. 2002; 295(2):337-47. DOI: 10.1006/viro.2002.1407. View