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 (AdVP1-2B) 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 AdVP1-2B 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 AdVP1-2B 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 AdVP1-2B, and a third treatment with the same dose of AdVP1-2B 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.

► A recombinant adenovirus AdVP1-2B which carrying shRNAs targeted to VP1 and 2B genes of FMDV expressed in tandem was been constructed. ► Treatment with AdVP1-2B both before and after FMDV infection, the FMDV RNA transcripts could not be detected within 48 h post-challenge. ► All guinea pigs were protected within 3 days post challenge (d.p.c.) when they were injected twice with the same dose of AdVP1-2B, and a third vaccination with the same dose of AdVP1-2B at 3 d.p.c. was necessary to last up to 6 d.p.c.