Adenovirus-vectored shRNAs targeted to the highly conserved regions of VP1 and 2B in tandem inhibits replication of foot-and-mouth disease virus both in vitro and in vivo.
Foot-and-mouth disease is a highly contagious and economically important disease of cloven-hoofed animals. RNA interference (RNAi) can be used as a rapid and specific antiviral approach. It was shown that treatment with recombinant adenovirus (Ad(VP1-2B)) carrying shRNAs targeted to the VP1 and 2B genes of FMDV expressed in tandem had marked antiviral effects against FMDV both in IBRS-2 cells and guinea pigs. Treatment with Ad(VP1-2B) both before and after FMDV infection was most effective in IBRS-2 cells, as the FMDV RNA transcripts could not be detected within 48 h post-challenge (hpc), and the viral RNA copy number at 72 hpc was only 0.02% of that in the positive control group. Delivery of Ad(VP1-2B) reduced significantly the susceptibility of guinea pigs to FMDV infection. All guinea pigs were protected within 3 days post challenge (dpc) when they were injected twice with the same dose of Ad(VP1-2B), and a third treatment with the same dose of Ad(VP1-2B) at 3 dpc was necessary to confer longer lasting protection (up to 6 dpc). In conclusion, application of such a adenovirus vector to inhibit more than one viral gene may be an advantageous method for prevention and therapy of FMDV infection.
College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou, 510640, China.
Yan-Fang
YF
Xu
Hai-Yan
HY
Shen
Ming-Qiu
MQ
Zhao
Li-Jun
LJ
Chen
Yin-Guang
YG
Li
Ming
M
Liao
Jun-Tao
JT
Jia
Ying-Ran
YR
Lv
Lin
L
Yi
Jin-Ding
JD
Chen
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001688:Biological Products / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D005536:Foot-and-Mouth Disease / Q000517:prevention & control; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000254:growth & development*; D005822:Genetic Vectors; D006168:Guinea Pigs; D008297:Male; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000494:pharmacology; D016896:Treatment Outcome; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*
D000998:Antiviral Agents; D001688:Biological Products; D034741:RNA, Small Interfering; D014764:Viral Proteins