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Influence of pan-caspase inhibitors on coxsackievirus B3-infected CD19+ B lymphocytes

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Abstract

Coxsackievirus B3 (CVB3), together with other enteroviruses of the picornavirus family, is associated with a wide variety of acute and chronic forms of human diseases. Using the murine model of CVB3-caused myocarditis, this pathogen can be detected not only in solid organs but also in different types of immune cells, preferentially in B lymphocytes. Therefore, these cells could represent a non-cardiac virus reservoir and may play an important role with regard to viral dissemination in the infected host. In addition, the infection of specific immune cells might modulate the severity of tissue injury and the pattern of virus-caused pathology in susceptible or resistant individuals. In the present study it could be demonstrated that CVB3 was capable to infect productively a certain percentage of murine CD19+ B cells. In vivo studies revealed that CVB3 invaded murine CD19+ B cells during an acute infection. Three days p. i. approximately 0.5–1.0% of these cells were productively infected. This proportion could be decreased up to 45%, if 3 days p. i. mice were intravenously treated with the pan-caspase inhibitors Z-VAD-FMK or Q-VD-OPH. These data were compared with results obtained from CVB3-infected human Raji cells.

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References

  1. Matteucci D, Paglianti M, Giangregorio AM, Capobianchi MR, Dianzani F, Bendinelli M (1985) Group B coxsackieviruses readily establish persistent infections in human lymphoid cell lines. J Virol 56:651–654

    PubMed  CAS  Google Scholar 

  2. Vuorinen T, Vainionpaa R, Kettinen H, Hyypia T (1994) Coxsackievirus B3 infection in human leukocytes and lymphoid cell lines. Blood 84:823–829

    PubMed  CAS  Google Scholar 

  3. Vuorinen T, Vainionpaa R, Vanharanta R, Hyypia T (1996) Susceptibility of human bone marrow cells and hematopoietic cell lines to coxsackievirus B3 infection. J Virol 70:9018–9023

    PubMed  CAS  Google Scholar 

  4. Vuorinen T, Vainionpaa R, Heino J, Hyypia T (1999) Enterovirus receptors and virus replication in human leukocytes. J Gen Virol 80(Pt 4):921–927

    PubMed  CAS  Google Scholar 

  5. Mena I, Perry CM, Harkins S, Rodriguez F, Gebhard J, Whitton JL (1999) The role of B lymphocytes in coxsackievirus B3 infection. Am J Pathol 155:1205–1215

    PubMed  CAS  Google Scholar 

  6. Klingel K, McManus BM, Kandolf R (1995) Enterovirus-infected immune cells of spleen and lymph nodes in the murine model of chronic myocarditis: a role in pathogenesis? Eur Heart J 16(Suppl O):42–45

    PubMed  Google Scholar 

  7. Anderson DR, Wilson JE, Carthy CM, Yang D, Kandolf R, McManus BM (1996) Direct interactions of coxsackievirus B3 with immune cells in the splenic compartment of mice susceptible or resistant to myocarditis. J Virol 70:4632–4645

    PubMed  CAS  Google Scholar 

  8. Kandolf R, Sauter M, Aepinus C, Schnorr JJ, Selinka HC, Klingel K (1999) Mechanisms and consequences of enterovirus persistence in cardiac myocytes and cells of the immune system. Virus Res 62:149–158

    Article  PubMed  CAS  Google Scholar 

  9. Henke A, Huber S, Stelzner A, Whitton JL (1995) The role of CD8+ T lymphocytes in coxsackievirus B3-induced myocarditis. J Virol 69:6720–6728

    PubMed  CAS  Google Scholar 

  10. Feuer R, Mena I, Pagarigan RR, Harkins S, Hassett DE, Whitton JL (2003) Coxsackievirus B3 and the neonatal CNS: the roles of stem cells, developing neurons, and apoptosis in infection, viral dissemination, and disease. Am J Pathol 163:1379–1393

    PubMed  CAS  Google Scholar 

  11. Saraste A, Arola A, Vuorinen T, et al (2003) Cardiomyocyte apoptosis in experimental coxsackievirus B3 myocarditis. Cardiovasc Pathol 12:255–262

    Article  PubMed  Google Scholar 

  12. Yuan JP, Zhao W, Wang HT, et al (2003) Coxsackievirus B3-induced apoptosis and caspase-3. Cell Res 13:203–209

    Article  PubMed  CAS  Google Scholar 

  13. Huber SA, Budd RC, Rossner K, Newell MK (1999) Apoptosis in coxsackievirus B3-induced myocarditis and dilated cardiomyopathy. Ann N Y Acad Sci 887:181–190

    Article  PubMed  CAS  Google Scholar 

  14. Carthy CM, Granville DJ, Watson KA, et al (1998) Caspase activation and specific cleavage of substrates after coxsackievirus B3-induced cytopathic effect in HeLa cells. J Virol 72:7669–7675

    PubMed  CAS  Google Scholar 

  15. Colston JT, Chandrasekar B, Freeman GL (1998) Expression of apoptosis-related proteins in experimental coxsackievirus myocarditis. Cardiovasc Res 38:158–168

    Article  PubMed  CAS  Google Scholar 

  16. Carthy CM, Yanagawa B, Luo H, et al (2003) Bcl-2 and Bcl-xL overexpression inhibits cytochrome c release, activation of multiple caspases, and virus release following coxsackievirus B3 infection. Virology 313:147–157

    Article  PubMed  CAS  Google Scholar 

  17. Henke A, Launhardt H, Klement K, Stelzner A, Zell R, Munder T (2000) Apoptosis in coxsackievirus B3-caused diseases: interaction between the capsid protein VP2 and the proapoptotic protein siva. J Virol 74:4284–4290

    Article  PubMed  CAS  Google Scholar 

  18. Henke A, Nestler M, Strunze S, et al (2001) The apoptotic capability of coxsackievirus B3 is influenced by the efficient interaction between the capsid protein VP2 and the proapoptotic host protein Siva. Virology 289:15–22

    Article  PubMed  CAS  Google Scholar 

  19. Martin U, Nestler M, Munder T, Zell R, Sigusch HH, Henke A (2004) Characterization of coxsackievirus B3-caused apoptosis under in vitro conditions. Med Microbiol Immunol (Berl) 193:133–139

    Article  CAS  Google Scholar 

  20. Cunningham MW, Antone SM, Gulizia JM, McManus BM, Fischetti VA, Gauntt CJ (1992) Cytotoxic and viral neutralizing antibodies crossreact with streptococcal M protein, enteroviruses, and human cardiac myosin. Proc Natl Acad Sci USA 89:1320–1324

    Article  PubMed  CAS  Google Scholar 

  21. Si X, Luo H, Morgan A, et al (2005) Stress-activated protein kinases are involved in coxsackievirus B3 viral progeny release. J Virol 79:13875–13881

    Article  PubMed  CAS  Google Scholar 

  22. Couderc T, Guivel-Benhassine F, Calaora V, Gosselin AS, Blondel B (2002) An ex vivo murine model to study poliovirus-induced apoptosis in nerve cells. J Gen Virol 83:1925–1930

    PubMed  CAS  Google Scholar 

  23. Deszcz L, Cencic R, Sousa C, Kuechler E, Skern T (2006) An antiviral peptide inhibitor that is active against picornavirus 2A proteinases but not cellular caspases. J Virol 80:9619–9627

    Article  PubMed  CAS  Google Scholar 

  24. Martin U, Jarasch N, Nestler M, et al (2007) Antiviral effects of pan-caspase inhibitors on the replication of coxsackievirus B3. Apoptosis 12:525–533

    Article  PubMed  CAS  Google Scholar 

  25. Knowlton KU, Jeon ES, Berkley N, Wessely R, Huber S (1996) A mutation in the puff region of VP2 attenuates the myocarditic phenotype of an infectious cDNA of the Woodruff variant of coxsackievirus B3. J Virol 70:7811–7818

    PubMed  CAS  Google Scholar 

  26. Slifka MK, Pagarigan R, Mena I, Feuer R, Whitton JL (2001) Using recombinant coxsackievirus B3 to evaluate the induction and protective efficacy of CD8+ T cells during picornavirus infection. J Virol 75:2377–2387

    Article  PubMed  CAS  Google Scholar 

  27. Caserta TM, Smith AN, Gultice AD, Reedy MA, Brown TL (2003) Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties. Apoptosis 8:345–352

    Article  PubMed  CAS  Google Scholar 

  28. Melnikov VY, Faubel S, Siegmund B, Lucia MS, Ljubanovic D, Edelstein CL (2002) Neutrophil-independent mechanisms of caspase-1- and IL-18-mediated ischemic acute tubular necrosis in mice. J Clin Invest 110:1083–1091

    Article  PubMed  CAS  Google Scholar 

  29. Seery JP, Cattell V, Watt FM (2001) Cutting edge: amelioration of kidney disease in a transgenic mouse model of lupus nephritis by administration of the caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-(beta-o-methyl)-fluoromethylketone. J Immunol 167:2452–2455

    PubMed  CAS  Google Scholar 

  30. Verstrepen WA, Kuhn S, Kockx MM, Van De Vyvere ME, Mertens AH (2001) Rapid detection of enterovirus RNA in cerebrospinal fluid specimens with a novel single-tube real-time reverse transcription-PCR assay. J Clin Microbiol 39:4093–4096

    Article  PubMed  CAS  Google Scholar 

  31. Kim KS, Tracy S, Tapprich W, et al (2005) 5′-Terminal deletions occur in coxsackievirus B3 during replication in murine hearts and cardiac myocyte cultures and correlate with encapsidation of negative-strand viral RNA. J Virol 79:7024–7041

    Article  PubMed  CAS  Google Scholar 

  32. Schotte P, Declercq W, Van Huffel S, Vandenabeele P, Beyaert R (1999) Non-specific effects of methyl ketone peptide inhibitors of caspases. FEBS Lett 442:117–121

    Article  PubMed  CAS  Google Scholar 

  33. Badorff C, Lee GH, Knowlton KU (2000) Enteroviral cardiomyopathy: bad news for the dystrophin-glycoprotein complex. Herz 25:227–232

    Article  PubMed  CAS  Google Scholar 

  34. DeBiasi RL, Robinson BA, Sherry B, et al (2004) Caspase inhibition protects against reovirus-induced myocardial injury in vitro and in vivo. J Virol 78:11040–11050

    Article  PubMed  CAS  Google Scholar 

  35. Catalan MP, Esteban J, Subira D, Egido J, Ortiz A (2003) Inhibition of caspases improves bacterial clearance in experimental peritonitis. Perit Dial Int 23:123–126

    PubMed  CAS  Google Scholar 

  36. Piguet PF, Kan CD, Vesin C (2002) Thrombocytopenia in an animal model of malaria is associated with an increased caspase-mediated death of thrombocytes. Apoptosis 7:91–98

    Article  PubMed  CAS  Google Scholar 

  37. Carlson DL, Willis MS, White DJ, Horton JW, Giroir BP (2005) Tumor necrosis factor-alpha-induced caspase activation mediates endotoxin-related cardiac dysfunction. Crit Care Med 33:1021–1028

    Article  PubMed  CAS  Google Scholar 

  38. Piguet PF, Vesin C, Donati Y, Barazzone C (1999) TNF-induced enterocyte apoptosis and detachment in mice: induction of caspases and prevention by a caspase inhibitor, ZVAD-fmk. Lab Invest 79:495–500

    PubMed  CAS  Google Scholar 

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Acknowledgement

This work was supported by Deutsche Forschungsgemeinschaft grant HE 2910/6-1.

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Authors and Affiliations

  1. Institute of Virology and Antiviral Therapy, Medical Center, Friedrich Schiller University, Hans-Knöll-Str. 2, 07745, Jena, Germany

    Nadine Jarasch, Ulrike Martin, Roland Zell, Peter Wutzler & Andreas Henke

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  1. Nadine Jarasch
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  2. Ulrike Martin
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  3. Roland Zell
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  4. Peter Wutzler
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  5. Andreas Henke
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Correspondence to Andreas Henke.

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Jarasch, N., Martin, U., Zell, R. et al. Influence of pan-caspase inhibitors on coxsackievirus B3-infected CD19+ B lymphocytes. Apoptosis 12, 1633–1643 (2007). https://doi.org/10.1007/s10495-007-0084-6

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  • DOI: https://doi.org/10.1007/s10495-007-0084-6

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