Lethal H5N1 influenza viruses escape host anti-viral cytokine responses
Lethal H5N1 influenza viruses escape host anti-viral cytokine responses
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DOI：
10.1038/nm757
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发表时间：
2002-09-01
期刊：
影响因子：
82.9
通讯作者：
Webster, RG
中科院分区：
文献类型：
--
作者：
Seo, SH;Hoffmann, E;Webster, RG
1997年传播给人类的H5N1流感病毒具有很强的毒性，但其对人类的毒性机制在很大程度上尚不清楚。在这里，我们表明，致命的H5N1流感病毒，不像其他人，禽流感和猪流感病毒，是抗干扰素和肿瘤坏死因子的抗病毒作用。H5N1病毒的非结构（NS）基因与这种耐药性有关。与感染野生型人H1N1流感病毒的猪相比，感染携带H5N1 NS基因的重组人H1N1流感病毒的猪经历了显著更大和更长时间的病毒血症、发热和体重减轻。这些效应需要NS1分子92位存在谷氨酸。这些发现可以解释H5N1流感病毒对人类的高毒力的机制。
The H5N1 influenza viruses transmitted to humans in 1997 were highly virulent, but the mechanism of their virulence in humans is largely unknown. Here we show that lethal H5N1 influenza viruses, unlike other human, avian and swine influenza viruses, are resistant to the antiviral effects of interferons and tumor necrosis factor. The nonstructural (NS) gene of H5N1 viruses is associated with this resistance. Pigs infected with recombinant human H1N1 influenza virus that carried the H5N1 NS gene experienced significantly greater and more prolonged viremia, fever and weight loss than did pigs infected with wild-type human H1N1 influenza virus. These effects required the presence of glutamic acid at position 92 of the NS1 molecule. These findings may explain the mechanism of the high virulence of H5N1 influenza viruses in humans.