RRC ID 36863
著者 Daidoji T, Watanabe Y, Ibrahim MS, Yasugi M, Maruyama H, Masuda T, Arai F, Ohba T, Honda A, Ikuta K, Nakaya T.
タイトル Avian Influenza Virus Infection of Immortalized Human Respiratory Epithelial Cells Depends upon a Delicate Balance between Hemagglutinin Acid Stability and Endosomal pH.
ジャーナル J Biol Chem
Abstract 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.
巻・号 290(17)
ページ 10627-42
公開日 2015-4-24
DOI 10.1074/jbc.M114.611327
PII S0021-9258(20)42595-5
PMID 25673693
PMC PMC4409229
MeSH Animals Birds Cell Line Clone Cells Dogs Endosomes / metabolism Endosomes / virology Hemagglutinin Glycoproteins, Influenza Virus / chemistry Hemagglutinin Glycoproteins, Influenza Virus / metabolism* Humans Hydrogen-Ion Concentration Influenza A Virus, H5N1 Subtype / pathogenicity* Influenza A Virus, H5N1 Subtype / physiology* Influenza in Birds / metabolism Influenza in Birds / transmission Influenza in Birds / virology Influenza, Human / metabolism Influenza, Human / transmission Influenza, Human / virology Protein Stability Receptors, Cell Surface / metabolism Respiratory Mucosa / metabolism Respiratory Mucosa / pathology Respiratory Mucosa / virology* Virulence / physiology Virus Internalization
IF 4.238
引用数 16
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 MDCK(RCB0995)