RNA interference targeting VP1 inhibits foot-and-mouth disease virus replication in BHK-21 cells and suckling mice.
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.
Chen
Weizao
W
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433, People's Republic of China.
Yan
Weiyao
W
Du
Qingyun
Q
Fei
Liang
L
Liu
Mingqiu
M
Ni
Zheng
Z
Sheng
Zutian
Z
Zheng
Zhaoxin
Z
D000818:Animals; D000833:Animals, Suckling; D036022:Capsid Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D005536:Foot-and-Mouth Disease / Q000821:virology*; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D034622:RNA Interference; D034741:RNA, Small Interfering; D014779:Virus Replication
D036022:Capsid Proteins; D034741:RNA, Small Interfering; C442501:VP1 protein, Foot-and-mouth disease virus