Emergence of HA mutants during influenza virus pneumonia.
Emergence of HA mutants during influenza virus pneumonia.
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DOI：
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发表时间：
2012
影响因子：
1.4
通讯作者：
M. Manríquez;A. Makino;Motoko Tanaka;Yasuhisa Abe;Hiroyuki Yoshida;I. Morioka;S. Arakawa;Y. Takeshima;K. Iwata;J. Takasaki;T. Manabe;T. Nakaya;S. Nakamura;A. H. Iglesias;Rosa Maria Rivera Rossales;E. P. Mirabal;T. Ito;T. Kitazawa;T. Oka;M. Yamashita;K. Kudo;K. Shinya
中科院分区：
文献类型：
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作者：
M. Manríquez;A. Makino;Motoko Tanaka;Yasuhisa Abe;Hiroyuki Yoshida;I. Morioka;S. Arakawa;Y. Takeshima;K. Iwata;J. Takasaki;T. Manabe;T. Nakaya;S. Nakamura;A. H. Iglesias;Rosa Maria Rivera Rossales;E. P. Mirabal;T. Ito;T. Kitazawa;T. Oka;M. Yamashita;K. Kudo;K. Shinya
在2009年流感大流行期间，与季节性流感病毒相比，病毒性肺炎病例数量明显增加。在大流行的早期阶段，在一些受影响更严重的患者中发现了病毒血凝素(HA)分子氨基酸222位的突变(D222G突变)，这种突变已知会改变病毒的受体识别特性。为了了解人类肺部出现突变氨基酸D222G的背景，我们对在大流行中死亡的墨西哥患者的肺标本进行了组织学检查。在墨西哥患者中，可以观察到肺泡II型肺泡细胞的显著再生和增生性变化，这些肺泡II型肺泡细胞在严重感染患者的呼吸道中表达鸟型唾液酸多糖受体。选择豚鼠建立感染模型，以最好地模拟人类重症肺炎患者的唾液酸分布，结果显示，与上呼吸道相比，下呼吸道的D222G突变增加，突变减少的时间延迟。我们的数据表明，肺炎肺中禽型唾液酸聚糖受体的优势可能有助于病毒HA突变体的出现。这些数据全面说明了突变在临床样本中出现的机制。
During the influenza pandemic of 2009, the number of viral pneumonia cases showed a marked increase in comparison with seasonal influenza viruses. Mutations at amino acid 222 (D222G mutations) in the virus hemagglutinin (HA) molecule, known to alter the receptor-recognition properties of the virus, were detected in a number of the more severely-affected patients in the early phases of the pandemic. To understand the background for the emergence of the mutant amino acid D222G in human lungs, we conducted histological examinations on lung specimens of patients from Mexico who had succumbed in the pandemic. Prominent regenerative and hyperplastic changes in the alveolar type II pneumocytes, which express avian-type sialoglycan receptors in the respiratory tract of severely affected individuals, were observed in the Mexican patients. An infection model utilizing guinea pigs, which was chosen in order to best simulate the sialic acid distribution of severe pneumonia in human patients, demonstrated an increase of D222G mutants and a delay in the diminution of mutants in the lower respiratory tract in comparison to the upper respiratory tract. Our data suggests that the predominance of avian-type sialoglycan receptors in the pneumonic lungs may contribute to the emergence of viral HA mutants. This data comprehensively illustrates the mechanisms for the emergence of mutants in the clinical samples.