title: Enhanced inhibition of foot-and-mouth disease virus by combinations of porcine interferon-α and antiviral agents.
abstract: Foot-and-mouth disease (FMD) is an economically significant animal disease because of the speed of its transmission. The current FMD vaccine provides no protection until 7days after the vaccination, which reduces its effectiveness in the case of an outbreak. Therefore, to find an alternative method of applying antiviral agents for rapid and enhanced inhibition of the FMD virus (FMDV), we compared the antiviral effects of promising antiviral agents and attempted to apply them in combination. First, we measured and compared the 50% effective concentration (EC(50)) to the mean inhibition effects of FMDV, and the 50% cytotoxic concentration (CC(50)) to the mean cytotoxicity of antiviral agents such as ribavirin, guanidine-hydrochloride (guanidine-HCl), 6-azauridine, and recombinant adenovirus expressing three small interference RNAs (Ad-siRNA) or porcine interferon-α (Ad-porcine IFN-α) in swine kidney cells (IBRS-2). The selectivity indices of ribavirin (35.2) and 6-azauridine (34.6) were higher than that of guanidine-HCl (26.9). The selectivity indices of Ad-siRNA or Ad-porcine IFN-α were 7×10(3) or 7×10(4) based on the adenoviral titer. Next, we tested the combined effects of the FMDV inhibition agents. Enhanced inhibition effects were observed in the IBRS-2 cells and in suckling mice from the combination of Ad-porcine IFN-α and Ad-siRNA or ribavirin. The combined application of these recombinant adenoviruses and ribavirin may enhance their inhibitory effect on FMDV and overcome FMDV resistance against antiviral agents.
authors.affiliation: Foot-and-Mouth Disease Division, Animal, Plant and Fisheries Quarantine and Inspection Agency, Ministry for Food, Agriculture, Forestry and Fisheries, 175 Anyang-ro, Manan-gu, Anyang-si, Gyeonggi-do, Republic of Korea. beliefsk@korea.kr
authors.forename: Su-Mi
authors.initials: SM
authors.lastname: Kim
authors.forename: Jong-Hyeon
authors.initials: JH
authors.lastname: Park
authors.forename: Kwang-Nyeong
authors.initials: KN
authors.lastname: Lee
authors.forename: Se-Kyung
authors.initials: SK
authors.lastname: Kim
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Ko
authors.forename: Hyang-Sim
authors.initials: HS
authors.lastname: Lee
authors.forename: In-Soo
authors.initials: IS
authors.lastname: Cho
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005536:Foot-and-Mouth Disease / Q000188:drug therapy; D029544:Foot-and-Mouth Disease Virus / Q000187:drug effects*; D016898:Interferon-alpha / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D013552:Swine; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha