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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus
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Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus

机译：现有的抗病毒药对具有1918年大流行病毒基因的流感病毒有效

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The 1918 influenza pandemic caused more than 20 million deaths worldwide. Thus, the potential impact of a re-emergent 1918 or 1918-like influenza virus, whether through natural means or as a result of bioterrorism, is of significant concern. The genetic determinants of the virulence of the 1918 virus have not been defined yet, nor have specific clinical prophylaxis and/or treatment interventions that would be effective against a re-emergent 1918 or 1918-like virus been identified. Based on the reported nucleotide sequences, we have reconstructed the hemagglutinin (HA), neur-aminidase (NA), and matrix (M) genes of the 1918 virus. Under biosafety level 3 (agricultural) conditions, we have generated recombinant influenza viruses bearing the 1918 HA, NA, or M segments. Strikingly, recombinant viruses possessing both the 1918 HA and 1918 NA were virulent in mice. In contrast, a control virus with the HA and NA from a more recent human isolate was unable to kill mice at any dose tested. The recombinant viruses were also tested for their sensitivity to U.S. Food and Drug Administration-approved antiinfluenza virus drugs in vitro and in vivo. Recombinant viruses possessing the 1918 NA or both the 1918 HA and 1918 NA were inhibited effectively in both tissue culture and mice by the NA inhibitors, zanamivir and oseltamivir. A recombinant virus possessing the 1918 M segment was inhibited effectively both in tissue culture and in vivo by the M2 ion-channel inhibitors amantadine and rimantadine. These data suggest that current antiviral strategies would be effective in curbing the dangers of a re-emergent 1918 or 1918-like virus.
机译：1918年的流感大流行在全球造成超过2000万人死亡。因此，无论是通过自然手段还是由于生物恐怖主义，重新出现的1918或1918样流感病毒的潜在影响都引起人们的极大关注。尚未确定1918病毒毒力的遗传决定因素，也没有确定对重新出现的1918或1918样病毒有效的特定临床预防和/或治疗干预措施。根据已报道的核苷酸序列，我们重建了1918年病毒的血凝素（HA），神经酰胺酶（NA）和基质（M）基因。在生物安全级别3（农业）条件下，我们已经产生了带有1918 HA，NA或M片段的重组流感病毒。令人惊讶的是，同时具有1918 HA和1918 NA的重组病毒在小鼠中具有毒性。相反，来自较新的人类分离株的具有HA和NA的对照病毒无法以任何测试剂量杀死小鼠。还测试了重组病毒在体外和体内对美国食品药品管理局批准的抗流感病毒药物的敏感性。具有1918 NA或1918 HA和1918 NA的重组病毒在组织培养和小鼠中均被NA抑制剂扎那米韦和奥司他韦有效抑制。 M2离子通道抑制剂金刚烷胺和金刚乙胺在组织培养和体内均有效抑制了具有1918 M片段的重组病毒。这些数据表明，当前的抗病毒策略将有效地遏制1918或1918样病毒的复发。

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