High-Definition Analysis of Host Protein Stability during Human Cytomegalovirus Infection Reveals Antiviral Factors and Viral Evasion Mechanisms

被引：75

作者：

Nightingale, Katie ^{[1
]}

Lin, Kai-Min ^{[1
]}

Ravenhill, Benjamin J. ^{[1
]}

Davies, Colin ^{[1
]}

Nobre, Luis ^{[1
]}

Fielding, Ceri A. ^{[2
]}

Ruckova, Eva ^{[3
]}

Fletcher-Etherington, Alice ^{[1
]}

Soday, Lior ^{[1
]}

Nichols, Hester ^{[2
]}

Sugrue, Daniel ^{[2
]}

Wang, Eddie C. Y. ^{[2
]}

Moreno, Pablo ^{[1
]}

Umrania, Yagnesh ^{[1
]}

Huttlin, Edward L. ^{[5
]}

Antrobus, Robin ^{[1
]}

Davison, Andrew J. ^{[4
]}

Wilkinson, Gavin W. G. ^{[2
]}

Stanton, Richard J. ^{[2
]}

Tomasec, Peter ^{[2
]}

Weekes, Michael P. ^{[1
]}

机构：

[1] Univ Cambridge, Cambridge Inst Med Res, Hills Rd, Cambridge CB2 0XY, England

[2] Cardiff Univ, Sch Med, Div Infect & Immun, Henry Wellcome Bldg,Heath Pk, Cardiff CF14 4XN, S Glam, Wales

[3] Masaryk Mem Canc Inst, Reg Ctr Appl Mol Oncol RECAMO, Zluty Kopec 7, Brno 65653, Czech Republic

[4] Univ Glasgow, MRC, Ctr Virus Res, Sir Michael Stoker Bldg,464 Bearsden Rd, Glasgow G61 1QH, Lanark, Scotland

[5] Harvard Med Sch, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA

来源：

CELL HOST & MICROBE | 2018年 / 24卷 / 03期

基金：

英国惠康基金;

关键词：

PROTEOMIC MAP; HUMAN HLTF; GENE; REPLICATION; EXPRESSION; HIV-1; DNA; DEGRADATION; DESTRUCTION; COMPONENT;

D O I：

10.1016/j.chom.2018.07.011

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Human cytomegalovirus (HCMV) is an important pathogen with multiple immune evasion strategies, including virally facilitated degradation of host antiviral restriction factors. Here, we describe a multiplexed approach to discover proteins with innate immune function on the basis of active degradation by the proteasome or lysosome during early-phase HCMV infection. Using three orthogonal proteomic/ transcriptomic screens to quantify protein degradation, with high confidence we identified 35 proteins enriched in antiviral restriction factors. A final screen employed a comprehensive panel of viral mutants to predict viral genes that target >250 human proteins. This approach revealed that helicase-like transcription factor (HLTF), a DNA helicase important in DNA repair, potently inhibits early viral gene expression but is rapidly degraded during infection. The functionally unknown HCMV protein UL145 facilitates HLTF degradation by recruiting the Cullin4 E3 ligase complex. Our approach and data will enable further identifications of innate pathways targeted by HCMV and other viruses.

引用

页码：447 / +

页数：25

共 33 条

[31] Absence of IE1 p72 protein function during low-multiplicity infection by human cytomegalovirus results in a broad block to viral delayed-early gene expression
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[32] Intracellular Trafficking of the Human CytomegalovirusEncoded 7-trans-Membrane Protein Homologs pUS27 and pUL78 during Viral Infection: A Comparative Analysis
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[33] Quantitative Proteomic Analysis of the Influenza A Virus Nonstructural Proteins NS1 and NS2 during Natural Cell Infection Identifies PACT as an NS1 Target Protein and Antiviral Host Factor
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Van Phan
Hrincius, Eike R.
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JOURNAL OF VIROLOGY, 2014, 88 (16) : 9038 - 9048

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