Enhanced inhibition of foot-and-mouth disease virus by combinations of porcine interferon-α and antiviral agents.
Enhanced inhibition of foot-and-mouth disease virus by combinations of porcine interferon-α and antiviral agents.
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DOI：
10.1016/j.antiviral.2012.09.009
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发表时间：
2012-11
影响因子：
7.6
通讯作者：
Cho IS
中科院分区：
文献类型：
--
作者：
Kim SM;Park JH;Lee KN;Kim SK;Ko YJ;Lee HS;Cho IS
我们测量了五种已知或潜在的抗病毒药物的EC 50和CC 50。结果表明，6-氮尿苷具有明显的抗病毒作用。我们测试了这两种抗病毒药物的联合作用。病毒唑可增强猪α-干扰素腺病毒的抗病毒作用。结果表明，Ad-IFN-α和Ad-siRNA均能增强猪IFN-α的抗病毒作用。口蹄疫（FMD）是一种经济上重要的动物疾病，因为它的传播速度。目前的口蹄疫疫苗在接种后7天才提供保护，这降低了其在爆发情况下的有效性。因此，为了找到一种应用抗病毒剂快速和增强抑制FMD病毒（FMDV）的替代方法，我们比较了有前途的抗病毒剂的抗病毒效果，并试图将它们组合应用。首先测定并比较了病毒唑、盐酸胍等抗病毒药物对口蹄疫病毒的半数有效浓度（EC_（50））和半数细胞毒浓度（CC_（50））（盐酸胍），6-氮杂尿苷，以及在猪肾细胞（IBRS-2）中表达三种小干扰RNA（Ad-siRNA）或猪干扰素-α（Ad-porcine IFN-α）的重组腺病毒。病毒唑和6-氮杂尿苷的选择性指数分别为35.2和34.6，高于盐酸胍的选择性指数26.9。根据腺病毒滴度，Ad-siRNA和Ad-IFN-α的选择性指数分别为7 × 103和7 × 104。接下来，我们测试了FMDV抑制剂的组合效果。在IBRS-2细胞和乳鼠中观察到Ad-IFN-α与Ad-siRNA或利巴韦林联合的抑制作用增强。重组腺病毒与利巴韦林联合应用可增强其对口蹄疫病毒的抑制作用，克服口蹄疫病毒对抗病毒药的耐药性。
► We measured EC50 and CC50 of the five well-known or potential antiviral agents. ► The antiviral effect against of 6-Azauridine was demonstrated. ► We tested the combination effects of the pairs of antiviral agents. ► Enhanced antiviral effect of Ad-porcine IFN-α with Ribavirin was demonstrated. ► Enhanced antiviral effect of Ad-porcine IFN-α and Ad-siRNA was demonstrated. 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 7 days 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 (EC50) to the mean inhibition effects of FMDV, and the 50% cytotoxic concentration (CC50) 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 × 103 or 7 × 104 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.
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