Chickens Expressing IFIT5 Ameliorate Clinical Outcome and Pathology of Highly Pathogenic Avian Influenza and Velogenic Newcastle Disease Viruses.
Chickens Expressing IFIT5 Ameliorate Clinical Outcome and Pathology of Highly Pathogenic Avian Influenza and Velogenic Newcastle Disease Viruses.
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DOI：
10.3389/fimmu.2018.02025
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发表时间：
2018
影响因子：
7.3
通讯作者：
Munir M
中科院分区：
文献类型：
--
作者：
Rohaim MA;Santhakumar D;Naggar RFE;Iqbal M;Hussein HA;Munir M
先天抗病毒免疫通过感知病原体的分子结构，如病毒RNA，建立起抵御入侵病原体的第一道防线。这种先天免疫的抗病毒潜力主要归因于无数的干扰素刺激基因(ISGs)。在已有的ISGs中，我们先前已经证明，鸡干扰素诱导的含有四肽重复序列5的蛋白(ChIFIT5)的抗病毒潜力取决于它与含有病毒RNA的5‘PPP的相互作用潜力。在这里，我们使用基于禽肉瘤白血病病毒(RCAS)的基因转移系统培育了稳定表达chIFIT5的转基因鸡。高致病性禽流感病毒(HPAIV；H5N1)和新城疫病毒(VNDV；基因VII型)临床剂量(HPAIV：104，vNDV：105EID50)或新城疫病毒强毒株(vNDV，基因VII型)感染的转基因鸡对感染表现出明显的抵抗力。虽然转基因鸡不能承受这些病毒的致死量(HPAIV的EID50 105和vNDV的106 EID50)，但与非转基因对照鸡相比，临床疾病和死亡率、病毒脱落和组织损伤的水平延迟和较低。这些观察表明，仅有chIFIT5的稳定表达可能不足以提供对这些高毒力病毒的无菌保护；然而，它足以改善这些RNA病毒的临床结果。这些发现提出了先天免疫基因在赋予鸡对引起动物和人类严重疾病的高致病性和人畜共患病毒病原体的遗传抵抗力方面的潜力。
Innate antiviral immunity establishes first line of defense against invading pathogens through sensing their molecular structures such as viral RNA. This antiviral potential of innate immunity is mainly attributed to a myriad of IFN-stimulated genes (ISGs). Amongst well-characterized ISGs, we have previously shown that antiviral potential of chicken IFN-induced proteins with tetratricopeptides repeats 5 (chIFIT5) is determined by its interaction potential with 5′ppp containing viral RNA. Here, we generated transgenic chickens using avian sarcoma-leukosis virus (RCAS)-based gene transfer system that constitutively and stably express chIFIT5. The transgenic chickens infected with clinical dose (EID50 104 for HPAIV and 105 EID50 for vNDV) of high pathogenicity avian influenza virus (HPAIV; H5N1) or velogenic strain of Newcastle disease virus (vNDV; Genotype VII) showed marked resistance against infections. While transgenic chickens failed to sustain a lethal dose of these viruses (EID50 105 for HPAIV and 106 EID50 for vNDV), a delayed and lower level of clinical disease and mortality, reduced virus shedding and tissue damage was observed compared to non-transgenic control chickens. These observations suggest that stable expression of chIFIT5 alone is potentially insufficient in providing sterile protection against these highly virulent viruses; however, it is sufficient to ameliorate the clinical outcome of these RNA viruses. These findings propose the potential of innate immune genes in conferring genetic resistance in chickens against highly pathogenic and zoonotic viral pathogens causing sever disease in both animals and humans.
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鸟类干扰素及其抗病毒效应子。
影响因子：
7.3
作者：
Santhakumar D;Rubbenstroth D;Martinez-Sobrido L;Munir M
通讯作者：
Munir M
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影响因子：
5.4
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通讯作者：
Staeheli, Peter
影响因子：
5.4
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通讯作者：
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