Meta- and Orthogonal Integration of Influenza "OMICs'' Data Defines a Role for UBR4 in Virus Budding

被引：733

作者：

Tripathi, Shashank ^{[1
,2
]}

Pohl, Marie O. ^{[3
]}

Zhou, Yingyao ^{[4
]}

Rodriguez-Frandsen, Ariel ^{[5
]}

Wang, Guojun ^{[1
]}

Stein, David A. ^{[6
]}

Moulton, Hong M. ^{[6
]}

DeJesus, Paul ^{[5
]}

Che, Jianwei ^{[4
]}

Mulder, Lubbertus C. F. ^{[1
]}

Yangueez, Emilio ^{[3
]}

Andenmatten, Dario ^{[3
]}

Pache, Lars ^{[5
]}

Manicassamy, Balaji ^{[1
]}

Albrecht, Randy A. ^{[1
]}

Gonzalez, Maria G. ^{[1
]}

Nguyen, Quy ^{[5
]}

Brass, Abraham ^{[7
]}

Elledge, Stephen ^{[8
,9
]}

White, Michael ^{[10
]}

Shapira, Sagi ^{[11
,12
]}

Hacohen, Nir ^{[13
]}

Karlas, Alexander ^{[14
]}

Meyer, Thomas F. ^{[14
]}

Shales, Michael ^{[15
]}

Gatorano, Andre ^{[5
]}

Johnson, Jeffrey R. ^{[15
]}

Jang, Gwen ^{[15
]}

Johnson, Tasha ^{[15
]}

Verschueren, Erik ^{[15
]}

Sanders, Doug ^{[15
]}

Krogan, Nevan ^{[15
]}

Shaw, Megan

Koenig, Renate ^{[5
,16
,17
]}

Stertz, Silke

Garcia-Sastre, Adolfo ^{[1
,2
,18
]}

Chanda, Sumit K. ^{[5
]}

机构：

[1] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA

[3] Univ Zurich, Inst Med Virol, CH-8057 Zurich, Switzerland

[4] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA

[5] Sanford Burnham Prebys Med Discovery Inst, Immun & Pathogenesis Program, Infect & Inflammatory Dis Ctr, La Jolla, CA 92037 USA

[6] Oregon State Univ, Coll Vet Med, Dept Biomed Sci, Corvallis, OR 97331 USA

[7] Univ Massachusetts, Sch Med, Microbiol & Physiol Syst MaPS Dept, Worcester, MA 01605 USA

[8] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Genet, Boston, MA 02127 USA

[9] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[10] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA

[11] Columbia Univ, Dept Syst Biol, New York, NY 10032 USA

[12] Dept Microbiol & Immunol, New York, NY 10032 USA

[13] Massachusetts Gen Hosp, Charlestown, MA 02129 USA

[14] Max Planck Inst Infect Biol, D-10117 Berlin, Germany

[15] Univ Calif San Francisco, San Francisco, CA 94158 USA

[16] Paul Ehrlich Inst, Host Pathogen Interact, D-63225 Langen, Germany

[17] German Ctr Infect Res DZIF, D-63225 Langen, Germany

[18] Icahn Sch Med Mt Sinai, Div Infect Dis, Dept Med, New York, NY 10029 USA

来源：

CELL HOST & MICROBE | 2015年 / 18卷 / 06期

基金：

瑞士国家科学基金会;

关键词：

HOST FACTORS; PROTEIN; SCREEN; ENTRY;

D O I：

10.1016/j.chom.2015.11.002

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Several systems-level datasets designed to dissect host-pathogen interactions during influenza A infection have been reported. However, apparent discordance among these data has hampered their full utility toward advancing mechanistic and therapeutic knowledge. To collectively reconcile these datasets, we performed a meta-analysis of data from eight published RNAi screens and integrated these data with three protein interaction datasets, including one generated within the context of this study. Further integration of these data with global virus-host interaction analyses revealed a functionally validated biochemical landscape of the influenza-host interface, which can be queried through a simplified and customizable web portal (http://www.metascape.org/IAV). Follow-up studies revealed that the putative ubiquitin ligase UBR4 associates with the viral M2 protein and promotes apical transport of viral proteins. Taken together, the integrative analysis of influenza OMICs datasets illuminates a viral-host network of high-confidence human proteins that are essential for influenza A virus replication.

引用

页码：723 / 735

页数：13

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