論文

査読有り
2015年4月

Avian Influenza Virus Infection of Immortalized Human Respiratory Epithelial Cells Depends upon a Delicate Balance between Hemagglutinin Acid Stability and Endosomal pH

JOURNAL OF BIOLOGICAL CHEMISTRY
  • Tomo Daidoji
  • ,
  • Yohei Watanabe
  • ,
  • Madiha S. Ibrahim
  • ,
  • Mayo Yasugi
  • ,
  • Hisataka Maruyama
  • ,
  • Taisuke Masuda
  • ,
  • Fumihito Arai
  • ,
  • Tomoyuki Ohba
  • ,
  • Ayae Honda
  • ,
  • Kazuyoshi Ikuta
  • ,
  • Takaaki Nakaya

290
17
開始ページ
10627
終了ページ
10642
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1074/jbc.M114.611327
出版者・発行元
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

The highly pathogenic avian influenza (AI) virus, H5N1, is a serious threat to public health worldwide. Both the currently circulating H5N1 and previously circulating AI viruses recognize avian-type receptors; however, only the H5N1 is highly infectious and virulent in humans. The mechanism(s) underlying this difference in infectivity remains unclear. The aim of this study was to clarify the mechanisms responsible for the difference in infectivity between the current and previously circulating strains. Primary human small airway epithelial cells (SAECs) were transformed with the SV40 large T-antigen to establish a series of clones (SAEC-Ts). These clones were then used to test the infectivity of AI strains. Human SAEC-Ts could be broadly categorized into two different types based on their susceptibility (high or low) to the viruses. SAEC-T clones were poorly susceptible to previously circulating AI but were completely susceptible to the currently circulating H5N1. The hemagglutinin (HA) of the current H5N1 virus showed greater membrane fusion activity at higher pH levels than that of previous AI viruses, resulting in broader cell tropism. Moreover, the endosomal pH was lower in high susceptibility SAEC-T clones than that in low susceptibility SAEC-T clones. Taken together, the results of this study suggest that the infectivity of AI viruses, including H5N1, depends upon a delicate balance between the acid sensitivity of the viral HA and the pH within the endosomes of the target cell. Thus, one of the mechanisms underlying H5N1 pathogenesis in humans relies on its ability to fuse efficiently with the endosomes in human airway epithelial cells.

Web of Science ® 被引用回数 : 17

リンク情報
DOI
https://doi.org/10.1074/jbc.M114.611327
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25673693
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000353404500005&DestApp=WOS_CPL

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