PLoS Pathogens：禽流感病毒出现危险变异

生物谷

    美国一所大学的科学家10月4日说，Ｈ５Ｎ１型禽流感病毒已经出现危险变异，更适于在人体内生存，但还没有转变为可以在人类间传播的病毒。

    美国威斯康星－麦迪逊大学博士川刚吉广（音译）负责这一研究，并将研究报告发表在最新一期《美国科学公共图书馆病毒学》PLoS Pathogens杂志上。

    “我们已经检测到禽流感病毒的一种特殊变异，它能使病毒适应人类上呼吸道的生存环境，”川刚接受路透社记者电话采访时说，“我们并不想惊吓公众，但人们对正在发生什么应当心中有数。”

    川刚说，鸟类体温大多在４１摄氏度，人类体温一般为３７摄氏度，而流感病毒进入人体的最主要渠道——鼻喉部位的体温一般为３３摄氏度，因此禽流感病毒通常难以在人体鼻喉内生存。然而，新的变异让Ｈ５Ｎ１型禽流感病毒能够在更低温度下存活。

    川刚还说，近期他与同事在欧洲与非洲提取的禽流感病毒样本中，全部发现了这种变异迹象，“它们更近似于人类流感病毒”。Ｈ５Ｎ１型禽流感病毒最早出现在亚洲，后借鸟类迁徙传播到非洲和欧洲。

    不过，川刚认为Ｈ５Ｎ１型禽流感病毒尚未出现其他变异迹象。“显然需要更多变异（才能成为可在人类间传播的禽流感病毒）。我们不知道到那一步还需要多少次变异。”

原始出处:

PLoS Pathogens

Received: June 7, 2007; Accepted: August 10, 2007; Published: October 5, 2007

A Single Mutation in the PB1-F2 of H5N1 (HK/97) and 1918 Influenza A Viruses Contributes to Increased Virulence

Gina M. Conenello1, Dmitriy Zamarin1, Lucy A. Perrone2, Terrence Tumpey2, Peter Palese1,3*

1 Department of Microbiology, Mount Sinai School of Medicine, New York, New York, United States of America, 2 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America, 3 Department of Medicine, Mount Sinai School of Medicine, New York, New York, United States of America

The proapoptotic PB1-F2 protein of influenza A viruses has been shown to contribute to pathogenesis in the mouse model. Expression of full-length PB1-F2 increases the pathogenesis of the influenza A virus, causing weight loss, slower viral clearance, and increased viral titers in the lungs. After comparing viruses from the Hong Kong 1997 H5N1 outbreak, one amino acid change (N66S) was found in the PB1-F2 sequence at position 66 that correlated with pathogenicity. This same amino acid change (N66S) was also found in the PB1-F2 protein of the 1918 pandemic A/Brevig Mission/18 virus. Two isogenic recombinant chimeric viruses were created with an influenza A/WSN/33 virus background containing the PB1 segment from the HK/156/97: WH and WH N66S. In mice infected with WH N66S virus there was increased pathogenicity as measured by weight loss and decreased survival, and a 100-fold increase in virus replication when compared to mice infected with the WH virus. The 1918 pandemic strain A/Brevig Mission/18 was reconstructed with a pathogenicity-reducing mutation in PB1-F2 (S66N). The resultant 1918 S66N virus was attenuated in mice having a 3-log lower 50% lethal dose and caused less morbidity and mortality in mice than the wild-type virus. Viral lung titers were also decreased in 1918 S66N–infected mice compared with wild-type 1918 virus–infected mice. In addition, both viruses with an S at position 66 (WH N66S and wt 1918) induced elevated levels of cytokines in the lungs of infected mice. Together, these data show that a single amino acid substitution in PB1-F2 can result in increased viral pathogenicity and could be one of the factors contributing to the high lethality seen with the 1918 pandemic virus.

全文链接：

http://pathogens.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.ppat.0030141

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