This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chen, W.
Right arrow Articles by Zheng, Z.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, W.
Right arrow Articles by Zheng, Z.

 Previous Article  |  Next Article 

Journal of Virology, April 2006, p. 3559-3566, Vol. 80, No. 7
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.7.3559-3566.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Adenovirus-Mediated RNA Interference against Foot-and-Mouth Disease Virus Infection both In Vitro and In Vivo

Weizao Chen,1 Mingqiu Liu,1 Ye Jiao,1 Weiyao Yan,1 Xuefeng Wei,2 Jiulian Chen,2 Liang Fei,1 Yang Liu,1 Xiaoping Zuo,2 Fugui Yang,2 Yonggan Lu,2 and Zhaoxin Zheng1*

State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433,1 Bio-pharmacy, Jinyu Group Co., Ltd., Inner Mongolia 010020, People's Republic of China2

Received 18 August 2005/ Accepted 9 January 2006

Foot-and-mouth disease virus (FMDV) infection is responsible for the heavy economic losses in stockbreeding each year. Because of the limited effectiveness of existing vaccines and antiviral drugs, the development of new strategies is needed. RNA interference (RNAi) is an effective means of suppressing virus replication in vitro. Here we demonstrate that treatment with recombinant, replication-defective human adenovirus type 5 (Ad5) expressing short-hairpin RNAs (shRNAs) directed against either structural protein 1D (Ad5-NT21) or polymerase 3D (Ad5-POL) of FMDV totally protects swine IBRS-2 cells from homologous FMDV infection, whereas only Ad5-POL inhibits heterologous FMDV replication. Moreover, delivery of these shRNAs significantly reduces the susceptibility of guinea pigs and swine to FMDV infection. Three of five guinea pigs inoculated with 106 PFU of Ad5-POL and challenged 24 h later with 50 50% infectious doses (ID50) of homologous virus were protected from the major clinical manifestation of disease: the appearance of vesicles on the feet. Two of three swine inoculated with an Ad5-NT21-Ad5-POL mixture containing 2 x 109 PFU each and challenged 24 h later with 100 ID50 of homologous virus were protected from the major clinical disease, but treatment with a higher dose of adenovirus mixture cannot promote protection of animals. The inhibition was rapid and specific because treatment with a control adenovirus construct (Ad5-LacZ) expressing Escherichia coli galactosidase-specific shRNA showed no marked antiviral activity. Our data highlight the in vivo potential of RNAi technology in the case of FMD.

* 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, April 2006, p. 3559-3566, Vol. 80, No. 7
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.7.3559-3566.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»