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) |