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A recombinant adenovirus bicistronically expressing porcine interferon-alpha and interferon-gamma enhances antiviral effects against foot-and-mouth disease virus

机译:双顺反子表达猪α-干扰素和γ-干扰素的重组腺病毒可增强针对口蹄疫病毒的抗病毒作用

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摘要

Foot-and-mouth disease (FMD) is a virulent and economically costly disease in domestic livestock. Since the current vaccine available against FMD provides no protection until 7 days postvaccination, the only alternative method to halt the spread of the FMD virus (FMDV) during outbreaks is by the application of anti-viral agents. The combination of recombinant adenovirus expressing type I interferon (IFN-alpha) and adenovirus expressing type IIIFN (IFN-gamma) has been reported to be an effective anti-viral treatment strategy against FMDV. Nevertheless, the recombinant adenovirus mixture may be inefficient because of the low anti-viral efficiency of IFN-gamma compared to that of IFN-alpha. In this study, we generated a recombinant adenovirus co-expressing porcine IFN-alpha and IFN-gamma in tandem using an FMDV 2A sequence to mediate effective cleavage of the two proteins (referred to as Ad-porcine IFN-alphalphagamma). We demonstrated that both recombinant porcine IFN-alpha and IFN-gamma were expressed and interferon stimulated gene (ISG)s related with IFN-alpha and IFN-gamma were induced in porcine kidney (IBRS-2) cells infected with Ad-porcine IFN-alphay. Additionally, the anti-viral effects of Ad-porcine IFN-alphay against FMDV were enhanced both in IBRS-2 cells and in CD-I (ICR) suckling mice compared to that of adenovirus expressing only a single protein. We propose that Ad-porcine IFN-alphay could be a rapid, highly efficient, convenient anti-viral agent against FMDV.
机译:口蹄疫(FMD)是家畜中的一种剧毒且经济上昂贵的疾病。由于目前可用的针对口蹄疫的疫苗直到接种后7天才提供保护,因此在爆发期间阻止口蹄疫病毒(FMDV)传播的唯一替代方法是应用抗病毒剂。据报道,表达I型干扰素(IFN-α)的重组腺病毒和表达IIIFN(IFN-γ)的腺病毒的组合是针对FMDV的有效抗病毒治疗策略。然而,由于与IFN-α相比IFN-γ的抗病毒效率低,重组腺病毒混合物可能是无效的。在这项研究中,我们使用FMDV 2A序列介导两种蛋白的有效切割(称为Ad-猪IFN-α-γ),串联生成共表达猪IFN-α和IFN-γ的重组腺病毒。我们证明重组猪IFN-α和IFN-γ均被表达,与IFN-α和IFN-γ相关的干扰素刺激基因(ISG)在感染Ad-猪IFN-的猪肾(IBRS-2)细胞中被诱导。阿尔法。另外,与仅表达单一蛋白的腺病毒相比,在IBRS-2细胞和CD-1(ICR)乳鼠中,Ad-猪IFN-α对FMDV的抗病毒作用均得到增强。我们提出,Ad-猪IFN-α可以作为快速,高效,方便的抗FMDV抗病毒剂。

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