Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells

Funke C, Farr M, Werner B, Dittmann S, Überla K, Piper C, Niehaus K, Horstkotte D (2010)
Journal of General Virology 91(8): 1959-1970.

Download
Es wurde kein Volltext hochgeladen. Nur Publikationsnachweis!
Zeitschriftenaufsatz | Veröffentlicht | Englisch
Autor
; ; ; ; ; ; ;
Abstract / Bemerkung
In viral myocarditis, adeno- and enteroviruses have most commonly been implicated as causes of infection. Both viruses require the human coxsackie-adenovirus receptor (CAR) to infect the myocardium. Due to its crucial role for viral entry, CAR-downregulation may lead to novel approaches for treatment for viral myocarditis. In this study, we report on pharmaceutical drug influences on CAR levels in human umbilical vein endothelial cells (HUVEC) and cervical carcinoma cells (HeLa) detected by immunoblotting, quantitative real time-PCR and cellular susceptibility to the cardiotropic coxsackie-B3 virus strain Nancy (CVB3). Our results indicate, for the first time, a dose-dependent CAR mRNA and protein downregulation upon Valsartan and Bosentan treatment. Most interestingly, drug-induced CAR diminution significantly reduced the viral load in CVB3-infected HUVEC. In order to assess the regulatory effects of both drugs in detail, we knocked down their protein targets, the G-protein coupled receptors angiotensin-II type-1 receptor (AT(1)R) and endothelin-1 type-A and -B receptors (ETAR/ETBR) in HUVEC. Receptor-specific gene silencing indicates that CAR gene expression is regulated by agonistic and antagonistic binding to ETBR, but not ETAR. In addition, neither stimulation nor inhibition of AT(1)R seemed to be involved in CAR gene regulatory processes. Our study indicates that Valsartan and Bosentan protected human endothelial cells from CVB3-infection. Therefore, besides their well-known anti-hypertensive effects these drugs may also protect the myocardium and other tissues from coxsackie- and adenoviral infection.
Erscheinungsjahr
Zeitschriftentitel
Journal of General Virology
Band
91
Ausgabe
8
Seite(n)
1959-1970
ISSN
eISSN
PUB-ID

Zitieren

Funke C, Farr M, Werner B, et al. Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells. Journal of General Virology. 2010;91(8):1959-1970.
Funke, C., Farr, M., Werner, B., Dittmann, S., Überla, K., Piper, C., Niehaus, K., et al. (2010). Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells. Journal of General Virology, 91(8), 1959-1970. doi:10.1099/vir.0.020065-0
Funke, C., Farr, M., Werner, B., Dittmann, S., Überla, K., Piper, C., Niehaus, K., and Horstkotte, D. (2010). Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells. Journal of General Virology 91, 1959-1970.
Funke, C., et al., 2010. Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells. Journal of General Virology, 91(8), p 1959-1970.
C. Funke, et al., “Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells”, Journal of General Virology, vol. 91, 2010, pp. 1959-1970.
Funke, C., Farr, M., Werner, B., Dittmann, S., Überla, K., Piper, C., Niehaus, K., Horstkotte, D.: Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells. Journal of General Virology. 91, 1959-1970 (2010).
Funke, Carsten, Farr, Martin, Werner, Bianca, Dittmann, Sven, Überla, Klaus, Piper, Cornelia, Niehaus, Karsten, and Horstkotte, Dieter. “Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells”. Journal of General Virology 91.8 (2010): 1959-1970.

4 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

Overcoming the Blood-Brain Barrier: The Role of Nanomaterials in Treating Neurological Diseases.
Furtado D, Björnmalm M, Ayton S, Bush AI, Kempe K, Caruso F., Adv Mater 30(46), 2018
PMID: 30066406
Effect of lovastatin on coxsackievirus B3 infection in human endothelial cells.
Werner B, Dittmann S, Funke C, Überla K, Piper C, Niehaus K, Horstkotte D, Farr M., Inflamm Res 63(4), 2014
PMID: 24316867
Characterization of coxsackievirus B3 replication in human umbilical vein endothelial cells.
Kühnl A, Rien C, Spengler K, Kryeziu N, Sauerbrei A, Heller R, Henke A., Med Microbiol Immunol 203(4), 2014
PMID: 24615265
Dioscin's antiviral effect in vitro.
Liu C, Wang Y, Wu C, Pei R, Song J, Chen S, Chen X., Virus Res 172(1-2), 2013
PMID: 23238077

39 References

Daten bereitgestellt von Europe PubMed Central.

Viral myocarditis and its sequelae.
Abelmann WH., Annu. Rev. Med. 24(), 1973
PMID: 4575848

Barst, Vasc Health Risk Manag 3(1), 2007
Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5.
Bergelson JM, Cunningham JA, Droguett G, Kurt-Jones EA, Krithivas A, Hong JS, Horwitz MS, Crowell RL, Finberg RW., Science 275(5304), 1997
PMID: 9036860
Receptor for the group B coxsackieviruses and adenoviruses: CAR.
Carson SD., Rev. Med. Virol. 11(4), 2001
PMID: 11479928
Coxsackievirus entry across epithelial tight junctions requires occludin and the small GTPases Rab34 and Rab5.
Coyne CB, Shen L, Turner JR, Bergelson JM., Cell Host Microbe 2(3), 2007
PMID: 18005733
Active myocarditis in the spectrum of acute dilated cardiomyopathies. Clinical features, histologic correlates, and clinical outcome.
Dec GW Jr, Palacios IF, Fallon JT, Aretz HT, Mills J, Lee DC, Johnson RA., N. Engl. J. Med. 312(14), 1985
PMID: 3974674
Acute viral myocarditis.
Dennert R, Crijns HJ, Heymans S., Eur. Heart J. 29(17), 2008
PMID: 18617482
Sudden death in young adults: a 25-year review of autopsies in military recruits.
Eckart RE, Scoville SL, Campbell CL, Shry EA, Stajduhar KC, Potter RN, Pearse LA, Virmani R., Ann. Intern. Med. 141(11), 2004
PMID: 15583223
The coxsackievirus and adenovirus receptor.
Freimuth P, Philipson L, Carson SD., Curr. Top. Microbiol. Immunol. 323(), 2008
PMID: 18357766
Significance of ventricular myocytes and nonmyocytes interaction during cardiocyte hypertrophy: evidence for endothelin-1 as a paracrine hypertrophic factor from cardiac nonmyocytes.
Harada M, Itoh H, Nakagawa O, Ogawa Y, Miyamoto Y, Kuwahara K, Ogawa E, Igaki T, Yamashita J, Masuda I, Yoshimasa T, Tanaka I, Saito Y, Nakao K., Circulation 96(10), 1997
PMID: 9396478
Biochemical and pharmacological profile of a potent and selective endothelin B-receptor antagonist, BQ-788.
Ishikawa K, Ihara M, Noguchi K, Mase T, Mino N, Saeki T, Fukuroda T, Fukami T, Ozaki S, Nagase T., Proc. Natl. Acad. Sci. U.S.A. 91(11), 1994
PMID: 8197152
Enhanced cellular receptor usage by a bioselected variant of coxsackievirus a21.
Johansson ES, Xing L, Cheng RH, Shafren DR., J. Virol. 78(22), 2004
PMID: 15507647
Tissue-specific deletion of the coxsackievirus and adenovirus receptor protects mice from virus-induced pancreatitis and myocarditis.
Kallewaard NL, Zhang L, Chen JW, Guttenberg M, Sanchez MD, Bergelson JM., Cell Host Microbe 6(1), 2009
PMID: 19616768
In situ detection of enteroviral genomes in myocardial cells by nucleic acid hybridization: an approach to the diagnosis of viral heart disease.
Kandolf R, Ameis D, Kirschner P, Canu A, Hofschneider PH., Proc. Natl. Acad. Sci. U.S.A. 84(17), 1987
PMID: 2819870
Virus receptor trap neutralizes coxsackievirus in experimental murine viral myocarditis.
Lim BK, Choi JH, Nam JH, Gil CO, Shin JO, Yun SH, Kim DK, Jeon ES., Cardiovasc. Res. 71(3), 2006
PMID: 16806133
The tight junction protein CAR regulates cardiac conduction and cell-cell communication.
Lisewski U, Shi Y, Wrackmeyer U, Fischer R, Chen C, Schirdewan A, Juttner R, Rathjen F, Poller W, Radke MH, Gotthardt M., J. Exp. Med. 205(10), 2008
PMID: 18794341
Presentation, patterns of myocardial damage, and clinical course of viral myocarditis.
Mahrholdt H, Wagner A, Deluigi CC, Kispert E, Hager S, Meinhardt G, Vogelsberg H, Fritz P, Dippon J, Bock CT, Klingel K, Kandolf R, Sechtem U., Circulation 114(15), 2006
PMID: 17015795
Bosentan enhances viral load via endothelin-1 receptor type-A-mediated p38 mitogen-activated protein kinase activation while improving cardiac function during coxsackievirus-induced myocarditis.
Marchant D, Dou Y, Luo H, Garmaroudi FS, McDonough JE, Si X, Walker E, Luo Z, Arner A, Hegele RG, Laher I, McManus BM., Circ. Res. 104(6), 2009
PMID: 19213955

AUTHOR UNKNOWN, Virology 271(), 2000
Influence of ACE-inhibition and mechanical unloading on the regulation of extracellular matrix proteins in the myocardium of heart transplantation candidates bridged by ventricular assist devices.
Milting H, Kassner A, Arusoglu L, Meyer HE, Morshuis M, Brendel R, Klauke B, El Banayosy A, Korfer R., Eur. J. Heart Fail. 8(3), 2005
PMID: 16309954
Human coxsackie-adenovirus receptor is colocalized with integrins alpha(v)beta(3) and alpha(v)beta(5) on the cardiomyocyte sarcolemma and upregulated in dilated cardiomyopathy: implications for cardiotropic viral infections.
Noutsias M, Fechner H, de Jonge H, Wang X, Dekkers D, Houtsmuller AB, Pauschinger M, Bergelson J, Warraich R, Yacoub M, Hetzer R, Lamers J, Schultheiss HP, Poller W., Circulation 104(3), 2001
PMID: 11457744
17 Beta-estradiol regulates the expression of endothelin receptor type B in the heart.
Nuedling S, van Eickels M, Allera A, Doevendans P, Meyer R, Vetter H, Grohe C., Br. J. Pharmacol. 140(1), 2003
PMID: 12967949
BQ-788, a selective endothelin ET(B) receptor antagonist.
Okada M, Nishikibe M., Cardiovasc Drug Rev 20(1), 2002
PMID: 12070534
Prevention of cardiac dysfunction in acute coxsackievirus B3 cardiomyopathy by inducible expression of a soluble coxsackievirus-adenovirus receptor.
Pinkert S, Westermann D, Wang X, Klingel K, Dorner A, Savvatis K, Grossl T, Krohn S, Tschope C, Zeichhardt H, Kotsch K, Weitmann K, Hoffmann W, Schultheiss HP, Spiller OB, Poller W, Fechner H., Circulation 120(23), 2009
PMID: 19933937
Epigenetic regulation of coxsackie and adenovirus receptor (CAR) gene promoter in urogenital cancer cells.
Pong RC, Lai YJ, Chen H, Okegawa T, Frenkel E, Sagalowsky A, Hsieh JT., Cancer Res. 63(24), 2003
PMID: 14695181
Cardiac deletion of the Coxsackievirus-adenovirus receptor abolishes Coxsackievirus B3 infection and prevents myocarditis in vivo.
Shi Y, Chen C, Lisewski U, Wrackmeyer U, Radke M, Westermann D, Sauter M, Tschope C, Poller W, Klingel K, Gotthardt M., J. Am. Coll. Cardiol. 53(14), 2009
PMID: 19341864
Measurement of protein using bicinchoninic acid.
Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC., Anal. Biochem. 150(1), 1985
PMID: 3843705
HCAR and MCAR: the human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses.
Tomko RP, Xu R, Philipson L., Proc. Natl. Acad. Sci. U.S.A. 94(7), 1997
PMID: 9096397
Viral myocarditis: from the perspective of the virus.
Yajima T, Knowlton KU., Circulation 119(19), 2009
PMID: 19451363
Soluble recombinant coxsackievirus and adenovirus receptor abrogates coxsackievirus b3-mediated pancreatitis and myocarditis in mice.
Yanagawa B, Spiller OB, Proctor DG, Choy J, Luo H, Zhang HM, Suarez A, Yang D, McManus BM., J. Infect. Dis. 189(8), 2004
PMID: 15073680
Heparan sulfates and coxsackievirus-adenovirus receptor: each one mediates coxsackievirus B3 PD infection.
Zautner AE, Korner U, Henke A, Badorff C, Schmidtke M., J. Virol. 77(18), 2003
PMID: 12941917

Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®

Quellen

PMID: 20392896
PubMed | Europe PMC

Suchen in

Google Scholar