Highly Pathogenic Avian Influenza Viruses Do Not Inhibit Interferon Synthesis in Infected Chickens but Can Override the Interferon-Induced Antiviral State
Highly Pathogenic Avian Influenza Viruses Do Not Inhibit Interferon Synthesis in Infected Chickens but Can Override the Interferon-Induced Antiviral State
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DOI：
10.1128/jvi.00063-11
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发表时间：
2011-08-01
影响因子：
5.4
通讯作者：
Staeheli, Peter
中科院分区：
文献类型：
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作者：
Penski, Nicola;Haertle, Sonja;Staeheli, Peter
从培养的鸡细胞和实验哺乳动物宿主的感染研究中，众所周知，流感病毒使用非结构蛋白1(NS1)来抑制干扰素(干扰素)的合成。然而，我们目前对病毒编码的NS1在鸡体内的作用的了解要有限得多。在此，我们报道了缺乏全功能NS1基因的H5N1和H7N7亚型高致病性禽流感病毒在5周龄雏鸡中的减毒效果。令人惊讶的是，在感染NS1突变体的病禽中，干扰素水平并不高于感染野生型病毒的病禽，这表明NS1不能抑制至少一个在体内产生大量细胞因子的感染鸡细胞群中的干扰素基因表达。为了解决流感病毒虽然能强烈激活天然免疫系统却对鸡具有高致病性的问题，我们确定了重组鸡α-干扰素(IFN-α)能否抑制高致病性禽流感病毒在培养的鸡细胞中的生长，以及它是否可以改善5周龄鸡的病毒诱导的疾病。我们发现，尽管干扰素治疗对低致病潜能的病毒有效，但它未能对高致病性病毒的攻击提供实质性的保护。综上所述，我们的数据表明，在鸡感染过程中，阻止干扰素的合成不是病毒NS1蛋白的主要作用。我们的结果进一步表明，病毒诱导的干扰素对鸡对高致病性流感病毒的抵抗力没有实质性的贡献。
From infection studies with cultured chicken cells and experimental mammalian hosts, it is well known that influenza viruses use the nonstructural protein 1 (NS1) to suppress the synthesis of interferon (IFN). However, our current knowledge regarding the in vivo role of virus-encoded NS1 in chickens is much more limited. Here, we report that highly pathogenic avian influenza viruses of subtypes H5N1 and H7N7 lacking fully functional NS1 genes were attenuated in 5-week-old chickens. Surprisingly, in diseased birds infected with NS1 mutants, the IFN levels were not higher than in diseased birds infected with wild-type virus, suggesting that NS1 cannot suppress IFN gene expression in at least one cell population of infected chickens that produces large amounts of the cytokine in vivo. To address the question of why influenza viruses are highly pathogenic in chickens although they strongly activate the innate immune system, we determined whether recombinant chicken alpha interferon (IFN-alpha) can inhibit the growth of highly pathogenic avian influenza viruses in cultured chicken cells and whether it can ameliorate virus-induced disease in 5-week-old birds. We found that IFN treatment failed to confer substantial protection against challenge with highly pathogenic viruses, although it was effective against viruses with low pathogenic potential. Taken together, our data demonstrate that preventing the synthesis of IFN is not the primary role of the viral NS1 protein during infection of chickens. Our results further suggest that virus-induced IFN does not contribute substantially to resistance of chickens against highly pathogenic influenza viruses.