| Item type |
文献 / Documents(1) |
| 公開日 |
2018-09-26 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.1371/journal.ppat.1007049 |
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関連名称 |
10.1371/journal.ppat.1007049 |
| 出版タイプ |
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出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
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タイトル |
Prion protein protects mice from lethal infection with influenza A viruses |
| 著者 |
千田, 淳司
原, 英之
矢野, 雅司
内山, 圭司
Das, Nandita Rani
高橋, 悦久
ミヤタ, ヒロノリ
富岡, 有紀子
イトウ, トシヒロ
木戸, 博
坂口, 末廣
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| 抄録 |
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内容記述 |
The cellular prion protein, designated PrPC, is a membrane glycoprotein expressed abundantly in brains and to a lesser extent in other tissues. Conformational conversion of PrPC into the amyloidogenic isoform is a key pathogenic event in prion diseases. However, the physiological functions of PrPC remain largely unknown, particularly in non-neuronal tissues. Here, we show that PrPC is expressed in lung epithelial cells, including alveolar type 1 and 2 cells and bronchiolar Clara cells. Compared with wild-type (WT) mice, PrPC-null mice (Prnp0/0) were highly susceptible to influenza A viruses (IAVs), with higher mortality. Infected Prnp0/0 lungs were severely injured, with higher inflammation and higher apoptosis of epithelial cells, and contained higher reactive oxygen species (ROS) than control WT lungs. Treatment with a ROS scavenger or an inhibitor of xanthine oxidase (XO), a major ROS-generating enzyme in IAV-infected lungs, rescued Prnp0/0 mice from the lethal infection with IAV. Moreover, Prnp0/0 mice transgenic for PrP with a deletion of the Cu-binding octapeptide repeat (OR) region, Tg(PrPΔOR)/Prnp0/0 mice, were also highly susceptible to IAV infection. These results indicate that PrPC has a protective role against lethal infection with IAVs through the Cu-binding OR region by reducing ROS in infected lungs. Cu content and the activity of anti-oxidant enzyme Cu/Zn-dependent superoxide dismutase, SOD1, were lower in Prnp0/0 and Tg (PrPΔOR)/Prnp0/0 lungs than in WT lungs. It is thus conceivable that PrPC functions to maintain Cu content and regulate SOD1 through the OR region in lungs, thereby reducing ROS in IAV-infected lungs and eventually protecting them from lethal infection with IAVs. Our current results highlight the role of PrPC in protection against IAV infection, and suggest that PrPC might be a novel target molecule for anti-influenza therapeutics. |
| 書誌情報 |
en : PLOS Pathogens
巻 14,
号 5,
p. e1007049,
発行日 2018-05-03
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
15537366 |
| 収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
15537374 |
| 収録物ID |
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収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA12072310 |
| 出版者 |
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出版者 |
PLOS |
| 権利情報 |
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|
権利情報 |
Copyright: © 2018 Chida et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| EID |
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|
識別子 |
342964 |
| 言語 |
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|
言語 |
eng |
plospathog_14_5_e1007049.pdf (11.7 MB)
