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Network-Guided Discovery of Influenza Virus Replication Host Factors
https://oist.repo.nii.ac.jp/records/915
https://oist.repo.nii.ac.jp/records/9154be6c24d-6e3f-41a3-b898-fcebcb8c5f46
名前 / ファイル | ライセンス | アクション |
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Ackerman-2018-Network-Guided Discovery of Infl (1.4 MB)
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Creative Commons
Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0/) |
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2019-06-06 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Network-Guided Discovery of Influenza Virus Replication Host Factors | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者(英) |
Ackerman, Emily E.
× Ackerman, Emily E.× Kawakami, Eiryo× Katoh, Manami× Watanabe, Tokiko× Watanabe, Shinji× Tomita, Yuriko× Lopes, Tiago J.× Matsuoka, Yukiko× Kitano, Hiroaki× Shoemaker, Jason E.× Kawaoka, Yoshihiro |
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書誌情報 |
en : mBio 巻 9, 号 6, p. e02002-18, 発行日 2018-12-18 |
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抄録 | ||||||
内容記述タイプ | Other | |||||
内容記述 | The positions of host factors required for viral replication within a human protein-protein interaction (PPI) network can be exploited to identify drug targets that are robust to drug-mediated selective pressure. Host factors can physically interact with viral proteins, be a component of virus-regulated pathways (where proteins do not interact with viral proteins), or be required for viral replication but unregulated by viruses. Here, we demonstrate a method of combining human PPI networks with virus-host PPI data to improve antiviral drug discovery for influenza viruses by identifying target host proteins. Analysis shows that influenza virus proteins physically interact with host proteins in network positions significant for information flow, even after the removal of known abundance-degree bias within PPI data. We have isolated a subnetwork of the human PPI network that connects virus-interacting host proteins to host factors that are important for influenza virus replication without physically interacting with viral proteins. The subnetwork is enriched for signaling and immune processes distinct from those associated with virus-interacting proteins. Selecting proteins based on subnetwork topology, we performed an siRNA screen to determine whether the subnetwork was enriched for virus replication host factors and whether network position within the subnetwork offers an advantage in prioritization of drug targets to control influenza virus replication. We found that the subnetwork is highly enriched for target host proteins-more so than the set of host factors that physically interact with viral proteins. Our findings demonstrate that network positions are a powerful predictor to guide antiviral drug candidate prioritization.IMPORTANCE Integrating virus-host interactions with host protein-protein interactions, we have created a method using these established network practices to identify host factors (i.e., proteins) that are likely candidates for antiviral drug targeting. We demonstrate that interaction cascades between host proteins that directly interact with viral proteins and host factors that are important to influenza virus replication are enriched for signaling and immune processes. Additionally, we show that host proteins that interact with viral proteins are in network locations of power. Finally, we demonstrate a new network methodology to predict novel host factors and validate predictions with an siRNA screen. Our results show that integrating virus-host proteins interactions is useful in the identification of antiviral drug target candidates. | |||||
出版者 | ||||||
出版者 | American Society for Microbiology | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 2150-7511 | |||||
PubMed番号 | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | PMID | |||||
関連識別子 | info:pmid/30563907 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | info:doi/10.1128/mBio.02002-18 | |||||
権利 | ||||||
権利情報 | © 2018 Ackerman et al. | |||||
情報源 | ||||||
関連名称 | https://creativecommons.org/licenses/by/4.0/ | |||||
関連サイト | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://mbio.asm.org/content/9/6/e02002-18 | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 |