A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells

Kuo Feng Weng, Chuan Tien Hung, Po Ting Hsieh, Mei Ling Li, Guang Wu Chen, Yu An Kung, Peng Nien Huang, Rei Lin Kuo, Li Lien Chen, Jing Yi Lin, Robert Y ung Liang Wang, Shu Jen Chen, Petrus Tang, Jim Tong Horng, Hsing I. Huang, Jen Ren Wang, David M. Ojcius, Gary Brewer, Shin Ru Shih

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22 Citations (Scopus)

Abstract

The roles of virus-derived small RNAs (vsRNAs) have been studied in plants and insects. However, the generation and function of small RNAs from cytoplasmic RNA viruses in mammalian cells remain unexplored. This study describes four vsRNAs that were detected in enterovirus 71-infected cells using next-generation sequencing and northern blots. Viral infection produced substantial levels (>10(5) copy numbers per cell) of vsRNA1, one of the four vsRNAs. We also demonstrated that Dicer is involved in vsRNA1 generation in infected cells. vsRNA1 overexpression inhibited viral translation and internal ribosomal entry site (IRES) activity in infected cells. Conversely, blocking vsRNA1 enhanced viral yield and viral protein synthesis. We also present evidence that vsRNA1 targets stem-loop II of the viral 5' untranslated region and inhibits the activity of the IRES through this sequence-specific targeting. Our study demonstrates the ability of a cytoplasmic RNA virus to generate functional vsRNA in mammalian cells. In addition, we also demonstrate a potential novel mechanism for a positive-stranded RNA virus to regulate viral translation: generating a vsRNA that targets the IRES.

Original languageEnglish
Pages (from-to)12789-12805
Number of pages17
JournalNucleic Acids Research
Volume42
Issue number20
DOIs
Publication statusPublished - Nov 10 2014

ASJC Scopus subject areas

  • Medicine(all)

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    Weng, K. F., Hung, C. T., Hsieh, P. T., Li, M. L., Chen, G. W., Kung, Y. A., Huang, P. N., Kuo, R. L., Chen, L. L., Lin, J. Y., Wang, R. Y. U. L., Chen, S. J., Tang, P., Horng, J. T., Huang, H. I., Wang, J. R., Ojcius, D. M., Brewer, G., & Shih, S. R. (2014). A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells. Nucleic Acids Research, 42(20), 12789-12805. https://doi.org/10.1093/nar/gku952