Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets.
Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets.
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DOI：
10.1038/nature10831
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发表时间：
2012-05-02
期刊：
影响因子：
64.8
通讯作者：
Kawaoka, Yoshihiro
中科院分区：
文献类型：
--
作者：
Imai, Masaki;Watanabe, Tokiko;Hatta, Masato;Das, Subash C.;Ozawa, Makoto;Shinya, Kyoko;Zhong, Gongxun;Hanson, Anthony;Katsura, Hiroaki;Watanabe, Shinji;Li, Chengjun;Kawakami, Eiryo;Yamada, Shinya;Kiso, Maki;Suzuki, Yasuo;Maher, Eileen A.;Neumann, Gabriele;Kawaoka, Yoshihiro
高致病性H5N1甲型禽流感病毒偶尔会感染人类，但目前不会在人类之间有效传播。病毒血凝素（HA）蛋白是已知的宿主范围决定因子，因为它介导病毒与宿主特异性细胞受体的结合。因此，在这里，我们评估了HA分子的变化，使H5 HA病毒能够在哺乳动物之间传播。我们在雪貂模型中发现了一种具有H5 HA的重组病毒，该病毒在2009年大流行H1N1病毒主干中具有四个突变，能够通过飞沫传播。可传播的H5重组病毒优先识别人型受体，在雪貂中有效复制，引起肺部病变和体重减轻，但不具有高致病性，也不导致死亡。这些结果表明H5透明质酸可以转化为支持病毒在哺乳动物中有效传播的透明质酸。然而，我们不知道本研究中发现的H5 HA的四种突变是否会使H5N1病毒完全具有传染性。其余七种病毒基因的遗传起源也可能对哺乳动物的传播性起关键作用。然而，随着H5N1病毒继续进化并感染人类，可能出现具有大流行潜力的H5N1病毒的受体结合变体，包括本文测试的禽人重组病毒。我们的研究结果强调了对携带H5 ha的病毒进行大流行防备的必要性，并将有助于个人在H5N1病毒流行地区进行监测，以识别预测分离株大流行潜力的关键残留，这将为有效对策的开发、生产和分发提供信息。
Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. The viral haemagglutinin (HA) protein is a known host range determinant since it mediates virus binding to host-specific cellular receptors. Here, we therefore assessed the molecular changes in HA that would allow an H5 HA-possessing virus to transmit among mammals. We identified a reassortant virus with H5 HA possessing four mutations in a 2009 pandemic H1N1 virus backbone capable of droplet transmission in a ferret model. The transmissible H5 reassortant virus preferentially recognized human-type receptors, replicated efficiently in ferrets, caused lung lesions and weight loss, but it was not highly pathogenic and did not cause mortality. These results suggest that H5 HA can convert to an HA that supports efficient viral transmission in mammals. However, we do not know whether the four mutations in the H5 HA identified in this study would render a wholly avian H5N1 virus transmissible. The genetic origin of the remaining seven viral genes may also critically contribute to transmissibility in mammals. Nevertheless, as H5N1 viruses continue to evolve and infect humans, receptor-binding variants of H5N1 viruses with pandemic potential, including avian-human reassortant viruses as tested here, may emerge. Our findings emphasize the need for pandemic preparedness for H5 HA-possessing viruses and will help individuals conducting surveillance in regions with circulating H5N1 viruses to recognize key residues that predict the pandemic potential of isolates, which will inform the development, production, and distribution of effective countermeasures.
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影响因子：
11.8
作者：
Nidom CA;Takano R;Yamada S;Sakai-Tagawa Y;Daulay S;Aswadi D;Suzuki T;Suzuki Y;Shinya K;Iwatsuki-Horimoto K;Muramoto Y;Kawaoka Y
通讯作者：
Kawaoka Y
影响因子：
3.7
作者：
Chen LM;Blixt O;Stevens J;Lipatov AS;Davis CT;Collins BE;Cox NJ;Paulson JC;Donis RO
通讯作者：
Donis RO
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.94.26.14306
发表时间：
1997-12-23
影响因子：
11.1
作者：
Carr, CM;Chaudhry, C;Kim, PS
通讯作者：
Kim, PS
影响因子：
3.7
作者：
Gambaryan, A;Tuzikov, A;Klimov, A
通讯作者：
Klimov, A