Tyrphostin AG1478 Inhibits Encephalomyocarditis Virus and Hepatitis C Virus by Targeting Phosphatidylinositol 4-Kinase IIIα

被引：16

作者：

Dorobantu, Cristina M. ^{[1
]}

Harak, Christian ^{[2
]}

Klein, Rahel ^{[2
]}

van der Linden, Lonneke ^{[3
,4
,5
]}

Strating, Jeroen R. P. M. ^{[1
]}

van der Schaar, Hilde M. ^{[1
]}

Lohmann, Volker ^{[2
]}

van Kuppeveld, Frank J. M. ^{[1
]}

机构：

[1] Univ Utrecht, Fac Vet Med, Dept Infect Dis & Immunol, Div Virol, Utrecht, Netherlands

[2] Heidelberg Univ, Dept Infect Dis Mol Virol, Heidelberg, Germany

[3] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Med Microbiol, Nijmegen, Netherlands

[4] Univ Leuven, Rega Inst Med Res, Lab Virol & Chemotherapy, Leuven, Belgium

[5] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, Lab Clin Virol, Amsterdam, Netherlands

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2016年 / 60卷 / 10期

关键词：

PLASMA-MEMBRANE; ENTEROVIRUS REPLICATION; RNA REPLICATION; LIPID KINASE; RECRUITMENT; BETA; PTDINS(4,5)P-2; TRAFFICKING; 4-PHOSPHATE; PTDINS4P;

D O I：

10.1128/AAC.01331-16

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Encephalomyocarditis virus (EMCV), like hepatitis C virus (HCV), requires phosphatidylinositol 4-kinase III alpha(PI4KA) for genome replication. Here, we demonstrate that tyrphostin AG1478, a known epidermal growth factor receptor (EGFR) inhibitor, also inhibits PI4KA activity, both in vitro and in cells. AG1478 impaired replication of EMCV and HCV but not that of an EMCV mutant previously shown to escape PI4KA inhibition. This work uncovers novel cellular and antiviral properties of AG1478, a compound previously regarded only as a cancer chemotherapy agent.

引用

页码：6402 / 6406

页数：5

共 31 条

[1] Unliganded epidermal growth factor receptor dimerization induced by direct interaction of quinazolines with the ATP binding site [J].

Arteaga, CL ;

Ramsey, TT ;

Shawver, LK ;

Guyer, CA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (37) :23247-23254

[2] A plasma membrane pool of phosphatidylinositol 4-phosphate is generated by phosphatidylinositol 4-kinase type-III alpha:: Studies with the PH domains of the oxysterol binding protein and FAPP1 [J].

Balla, A ;

Tuymetova, G ;

Tsiomenko, A ;

Várnai, P ;

Balla, T .

MOLECULAR BIOLOGY OF THE CELL, 2005, 16 (03) :1282-1295

[3] A Critical Role of a Cellular Membrane Traffic Protein in Poliovirus RNA Replication [J].

Belov, George A. ;

Feng, Qian ;

Nikovics, Krisztina ;

Jackson, Catherine L. ;

Ehrenfeld, Ellie .

PLOS PATHOGENS, 2008, 4 (11)

[4] Roles for endocytic trafficking and phosphatidylinositol 4-kinase III alpha in hepatitis C virus replication [J].

Berger, Kristi L. ;

Cooper, Jacob D. ;

Heaton, Nicholas S. ;

Yoon, Rosa ;

Oakland, Todd E. ;

Jordan, Tristan X. ;

Mateu, Guaniri ;

Grakoui, Arash ;

Randall, Glenn .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (18) :7577-7582

[5] Metabolism of Phosphatidylinositol 4-Kinase IIIα-Dependent PI4P Is Subverted by HCV and Is Targeted by a 4-Anilino Quinazoline with Antiviral Activity [J].

Bianco, Annalisa ;

Reghellin, Veronica ;

Donnici, Lorena ;

Fenu, Simone ;

Alvarez, Reinaldo ;

Baruffa, Chiara ;

Peri, Francesco ;

Pagani, Massimiliano ;

Abrignani, Sergio ;

Neddermann, Petra ;

De Francesco, Raffaele .

PLOS PATHOGENS, 2012, 8 (03)

[6] Pharmacological and Genetic Targeting of the PI4KA Enzyme Reveals Its Important Role in Maintaining Plasma Membrane Phosphatidylinositol 4-Phosphate and Phosphatidylinositol 4,5-Bisphosphate Levels [J].

Bojjireddy, Naveen ;

Botyanszki, Janos ;

Hammond, Gerald ;

Creech, Donald ;

Peterson, Richard ;

Kemp, Daniel C. ;

Snead, Mark ;

Brown, Randy ;

Morrison, Alastair ;

Wilson, Steve ;

Harrison, Steve ;

Moore, Chris ;

Balla, Tamas .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289 (09) :6120-6132

[7] Class III Phosphatidylinositol 4-Kinase Alpha and Beta Are Novel Host Factor Regulators of Hepatitis C Virus Replication [J].

Borawski, Jason ;

Troke, Philip ;

Puyang, Xiaoling ;

Gibaja, Veronica ;

Zhao, ShanChaun ;

Mickanin, Craig ;

Leighton-Davies, Juliet ;

Wilson, Christopher J. ;

Myer, Vic ;

CornellaTaracido, Ivan ;

Baryza, Jeremy ;

Tallarico, John ;

Joberty, Gerard ;

Bantscheff, Marcus ;

Schirle, Markus ;

Bouwmeester, Tewis ;

Mathy, Joanna E. ;

Lin, Kai ;

Compton, Teresa ;

Labow, Mark ;

Wiedmann, Brigitte ;

Gaither, L. Alex .

JOURNAL OF VIROLOGY, 2009, 83 (19) :10058-10074

[8] Phosphatidylinositol 4-kinases: Function, structure, and inhibition [J].

Boura, Evzen ;

Nencka, Radim .

EXPERIMENTAL CELL RESEARCH, 2015, 337 (02) :136-145

[9] Mutations in Encephalomyocarditis Virus 3A Protein Uncouple the Dependency of Genome Replication on Host Factors Phosphatidylinositol 4-Kinase IIIα and Oxysterol-Binding Protein [J].

Dorobantu, Cristina M. ;

Albulescu, Lucian ;

Lyoo, Heyrhyoung ;

van Kampen, Mirjam ;

De Francesco, Raffaele ;

Lohmann, Volker ;

Harak, Christian ;

van der Schaar, Hilde M. ;

Strating, Jeroen R. P. M. ;

Gorbalenya, Alexander E. ;

van Kuppeveld, Frank J. M. .

MSPHERE, 2016, 1 (03)

[10] Modulation of the Host Lipid Landscape to Promote RNA Virus Replication: The Picornavirus Encephalomyocarditis Virus Converges on the Pathway Used by Hepatitis C Virus [J].