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Journal of Virology, July 2004, p. 6900-6907, Vol. 78, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.13.6900-6907.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

RNA Interference Targeting VP1 Inhibits Foot-and-Mouth Disease Virus Replication in BHK-21 Cells and Suckling Mice

Weizao Chen,1 Weiyao Yan,1 Qingyun Du,2 Liang Fei,1 Mingqiu Liu,1 Zheng Ni,2 Zutian Sheng,2 and Zhaoxin Zheng1*

State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433,1 Institute of Biotechnology, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, People's Republic of China2

Received 19 November 2003/ Accepted 19 February 2004

RNA interference (RNAi) is a powerful tool to silence gene expression posttranscriptionally. In this study, we evaluated the antiviral potential of small interfering RNA (siRNA) targeting VP1 of foot-and-mouth disease virus (FMDV), which is essential during the life cycle of the virus and plays a key role in virus attachment to susceptible cells. We investigated in vivo the inhibitory effect of VP1-specific siRNAs on FMDV replication in BHK-21 cells and suckling mice, a commonly used small animal model. The results showed that transfection of siRNA-expressing plasmids gave an 80 to 90% reduction in the expression of FMDV VP1 in BHK-21 cells. Moreover, BHK-21 cells transiently transfected with siRNA-expressing plasmids were specifically resistant to FMDV infection when exposed to 100 50% tissue culture infective doses of virus, and the antiviral effects extended to almost 48 h postinfection. Furthermore, subcutaneous injection of siRNA-expressing plasmids in the neck made suckling mice significantly less susceptible to FMDV. In conclusion, our data suggests that RNAi may provide a viable therapeutic approach to treat FMDV infection.

* Corresponding author. Mailing address: State Key Laboratory of Genetic Engineering, Fudan University, 220 Handan Rd., Shanghai 200433, People's Republic of China. Phone: 86 (21) 65642504. Fax: 86 (21) 65642504. E-mail: zxzheng{at}fudan.edu.cn.

Journal of Virology, July 2004, p. 6900-6907, Vol. 78, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.13.6900-6907.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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