In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses.
In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses.
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甲型流感病毒导致局部或全球规模的反复暴发，可能对人类健康和全球经济造成严重后果。最近，发现了一种新的甲型流感病毒株，它会在人类中引起疾病并在人与人之间传播，这可能是因为对这种新病毒株的免疫力很低或根本没有。2009年6月11日，世界卫生组织宣布，由新病毒株引起的感染已达到大流行比例。新毒株的基因组片段被描述为H1N1亚型的甲型流感病毒，与猪病毒关系最密切。大多数人感染猪源H1N1流感病毒(S-OIV)似乎是轻微的；然而，超过50%的住院患者没有潜在的健康问题，这证明了S-OIV的致病潜力。为了更好地评估新病毒构成的风险，我们在体外和体内鉴定了美国首批S-OIV分离株之一A/加利福尼亚/04/09(H1N1；CA04)以及其他几个S-OIV分离株。在小鼠和雪貂身上，CA04和其他测试的S OIV分离株的复制效率高于目前流行的人类H1N1病毒。此外，CA04在非人类灵长类动物中有效复制，在受感染的小鼠、雪貂和非人类灵长类动物的肺部造成比目前流行的人类H1N1病毒更严重的病理损害，并在雪貂之间传播。在无特定病原体的小型猪中，CA04在没有临床症状的情况下复制。对不同年龄段的人血清的评估表明，感染与1918年流行的病毒在抗原性上密切相关的人H1N1病毒可以赋予CA04中和抗体活性。最后，我们表明CA04对批准的和实验性的抗病毒药物是敏感的，这表明这些化合物是对抗最近宣布的S-OIV大流行的第一道防线。
Influenza A viruses cause recurrent outbreaks of local or global scale with potentially severe consequences for human health and the global economy. Recently, a new strain of influenza A virus was detected that causes disease in and transmits among humans, probably owing to little or no pre-existing immunity to the new strain. On June 11, 2009, the WHO declared that the infections caused by the new strain had reached pandemic proportion. Characterized as an influenza A virus of the H1N1 subtype, the genomic segments of the new strain were most closely related to swine viruses. Most human infections with swine-origin H1N1 influenza viruses (S-OIVs) appear to be mild; however, more than 50% of hospitalized individuals do not have underlying health issues, attesting to the pathogenic potential of S-OIVs. To better assess the risk posed by the new virus, we characterized one of the first US S-OIV isolates, A/California/04/09 (H1N1; CA04), as well as several other S-OIV isolates, in vitro and in vivo. In mice and ferrets, CA04 and other S-OIV isolates tested replicate more efficiently than a currently circulating human H1N1 virus. In addition, CA04 replicates efficiently in nonhuman primates, causes more severe pathologic lesions in the lungs of infected mice, ferrets, and nonhuman primates than a currently circulating human H1N1 virus, and transmits among ferrets. In specific-pathogen free miniature pigs, CA04 replicates without clinical symptoms. The assessment of human sera from different age groups suggests that infection with human H1N1 viruses antigenically closely related to viruses circulating in 1918 confers neutralizing antibody activity to CA04. Finally, we show that CA04 is sensitive to approved and experimental antiviral drugs, suggesting these compounds as a first line of defence against the recently declared S-OIV pandemic.
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DOI：
10.4049/jimmunol.0801814
发表时间：
2009-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hamada H;Garcia-Hernandez Mde L;Reome JB;Misra SK;Strutt TM;McKinstry KK;Cooper AM;Swain SL;Dutton RW
通讯作者：
Dutton RW
影响因子：
9.4
作者：
Hatakeyama, S;Sakai-Tagawa, Y;Kawaoka, Y
通讯作者：
Kawaoka, Y
DOI：
10.1073/pnas.85.2.324
发表时间：
1988-01-01
影响因子：
11.1
作者：
KAWAOKA, Y;WEBSTER, RG
通讯作者：
WEBSTER, RG
影响因子：
5.4
作者：
Neumann, G;Ebihara, H;Kawaoka, Y
通讯作者：
Kawaoka, Y
影响因子：
5.4
作者：
Rimmelzwaan, GF;Kuiken, T;Osterhaus, ADME
通讯作者：
Osterhaus, ADME