This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 99/4/354    most recent 01.RES.0000237022.72726.01v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Esfandiarei, M. Articles by McManus, B. M. Search for Related Content PubMed PubMed Citation Articles by Esfandiarei, M. Articles by McManus, B. M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Medline Plus Health Information Cardiomyopathy Related Collections Infectious endocarditis Apoptosis Cell signalling/signal transduction Heart failure - basic studies Related Article

(Circulation Research. 2006;99:354.)
© 2006 American Heart Association, Inc.

Molecular Medicine

Novel Role for Integrin-Linked Kinase in Modulation of Coxsackievirus B3 Replication and Virus-Induced Cardiomyocyte Injury

Mitra Esfandiarei, Agripina Suarez, Ansel Amaral, Xiaoning Si, Maziar Rahmani, Shoukat Dedhar, Bruce M. McManus

From The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research/Providence Health Care Research Institute (M.E., A.S., A.A., X.S., M.R., B.M.M.), Department of Pathology and Laboratory Medicine; and Department of Biochemistry and Molecular Biology (S.D.), Department of Cancer Genetics, British Columbia Cancer Agency, University of British Columbia, Vancouver, Canada.

Correspondence to Dr Bruce M. McManus, The James Hogg iCAPTURE Centre/Providence Health Care Research Institute, UBC-St. Paul’s Hospital, Rm 388 Burrard West, 1081 Burrard St, Vancouver, British Columbia V6Z 1Y6, Canada. E-mail bmcmanus{at}mrl.ubc.ca

Viral myocarditis is a major cause of sudden cardiac death in children and young adults. Among viruses, coxsackievirus B3 (CVB3) is the most common agent for myocarditis. Recently, more consideration has been given to the role of signaling pathways in pathogenesis of enteroviral myocarditis, providing new platform for identifying a new potential therapeutic target for this, so far, incurable disease. Previously, we reported on the role of the protein kinase-B/Akt in CVB3 replication and virus-induced cell injury. Here, we report on regulation of virus-induced Akt activation by the integrin-linked kinase in infected mouse cardiomyocytes and HeLa cells. This study also presents the first observation that inhibition of ILK in CVB3-infected cells significantly improves the viability of infected cells, while blocking viral replication and virus release. Complementary experiments using a constitutively active form of Akt1 revealed that the observed protective effect of ILK inhibition is dependent on the associated downregulation of virus-induced Akt activation. To our knowledge, this is the first report of such beneficial effects of ILK inhibition in a viral infection model and conveys new insights in our efforts to characterize a novel therapeutic target for treatment of enteroviral myocarditis.

Key Words: viral myocarditis • CVB3 • integrin-linked kinase • cell death • PKB/Akt

Related Article:

Integrin-Linked Kinase Plays a Key Role in Coxsackievirus Replication

Charles J. Lowenstein
Circ. Res. 2006 99: 346-347. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				F. Acconcia, C. J. Barnes, R. R. Singh, A. H. Talukder, and R. Kumar Phosphorylation-dependent regulation of nuclear localization and functions of integrin-linked kinase PNAS, April 17, 2007; 104(16): 6782 - 6787. [Abstract] [Full Text] [PDF]

				C. J. Lowenstein Integrin-Linked Kinase Plays a Key Role in Coxsackievirus Replication Circ. Res., August 18, 2006; 99(4): 346 - 347. [Full Text] [PDF]