1887

Abstract

Variations in the cellular microenvironment affect the host's susceptibility to pathogens. Using glucose-6-phosphate dehydrogenase (G6PD)-deficient fibroblasts as a model, this study demonstrated that the cellular redox status affects infectivity as well as the outcome of enterovirus 71 (EV71) infection. Compared with their normal counterparts, G6PD-deficient cells supported EV71 replication more efficiently and showed greater cytopathic effect and loss of viability. Mechanistically, viral infection led to increased oxidative stress, as indicated by increased dichlorofluorescein fluorescence and a diminished ratio of glutathione (GSH) to its disulfide form (GSSG), with the effect being greater in G6PD-deficient cells. Exogenous expression of active G6PD in the deficient cells, which increased the intracellular GSH : GSSG ratio, suppressed the generation of viral progeny. Consistent with this, treatment with -acetylcysteine offered resistance to EV71 propagation and a cytoprotective effect on the infected cells. These findings support the notion that G6PD status, and thus redox balance, is an important determinant of enteroviral infection.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.2008/001404-0
2008-09-01
2024-04-26
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/9/2080.html?itemId=/content/journal/jgv/10.1099/vir.0.2008/001404-0&mimeType=html&fmt=ahah

References

  1. Agol V. I., Belov G. A., Bienz K., Egger D., Kolesnikova M. S., Raikhlin N. T., Romanova L. I., Smirnova E. A., Tolskaya E. A. 1998; Two types of death of poliovirus-infected cells: caspase involvement in the apoptosis but not cytopathic effect. Virology 252:343–353 [CrossRef]
    [Google Scholar]
  2. Beck M. A., Kolbeck P. C., Rohr L. H., Shi Q., Morris V. C., Levander O. A. 1994a; Benign human enterovirus becomes virulent in selenium-deficient mice. J Med Virol 43:166–170 [CrossRef]
    [Google Scholar]
  3. Beck M. A., Kolbeck P. C., Rohr L. H., Shi Q., Morris V. C., Levander O. A. 1994b; Vitamin E deficiency intensifies the myocardial injury of coxsackievirus B3 infection of mice. J Nutr 124:345–358
    [Google Scholar]
  4. Beck M. A., Handy J., Levander O. A. 2000; The role of oxidative stress in viral infections. Ann N Y Acad Sci 917:906–912
    [Google Scholar]
  5. Beck M. A., Nelson H. K., Shi Q., Van Dael P., Schiffrin E. J., Blum S., Barclay D., Levander O. A. 2001; Selenium deficiency increases the pathology of an influenza virus infection. FASEB J 15:1481–1483
    [Google Scholar]
  6. Beck M. A., Levander O. A., Handy J. 2003a; Selenium deficiency and viral infection. J Nutr 133:1463S–1467S
    [Google Scholar]
  7. Beck M. A., Williams-Toone D., Levander O. A. 2003b; Coxsackievirus B3-resistant mice become susceptible in Se/vitamin E deficiency. Free Radic Biol Med 34:1263–1270 [CrossRef]
    [Google Scholar]
  8. Beck M. A., Handy J., Levander O. A. 2004; Host nutritional status: the neglected virulence factor. Trends Microbiol 12:417–423 [CrossRef]
    [Google Scholar]
  9. Beck M. A., Shi Q., Morris V. C., Levander O. A. 2005; Benign coxsackievirus damages heart muscle in iron-loaded vitamin E-deficient mice. Free Radic Biol Med 38:112–116 [CrossRef]
    [Google Scholar]
  10. Beutler E. 1991; Glucose-6-phosphate dehydrogenase deficiency. N Engl J Med 324:169–174 [CrossRef]
    [Google Scholar]
  11. Bhaskaram P. 2001; Immunobiology of mild micronutrient deficiencies. Br J Nutr 85:Suppl. 2S75–S80 [CrossRef]
    [Google Scholar]
  12. Biagioli M. C., Kaul P., Singh I., Turner R. B. 1999; The role of oxidative stress in rhinovirus induced elaboration of IL-8 by respiratory epithelial cells. Free Radic Biol Med 26:454–462 [CrossRef]
    [Google Scholar]
  13. Cai J., Chen Y., Seth S., Furukawa S., Compans R. W., Jones D. P. 2003; Inhibition of influenza infection by glutathione. Free Radic Biol Med 34:928–936 [CrossRef]
    [Google Scholar]
  14. Cheng M. L., Ho H. Y., Liang C. M., Chou Y. H., Stern A., Lu F. J., Chiu D. T. 2000; Cellular glucose-6-phosphate dehydrogenase (G6PD) status modulates the effects of nitric oxide (NO) on human foreskin fibroblasts. FEBS Lett 475:257–262 [CrossRef]
    [Google Scholar]
  15. Cheng A. J., Chiu D. T., See L. C., Liao C. T., Chen I. H., Chang J. T. 2001; Poor prognosis in nasopharyngeal cancer patients with low glucose-6-phosphate-dehydrogenase activity. Jpn J Cancer Res 92:576–581 [CrossRef]
    [Google Scholar]
  16. Cheng M. L., Ho H. Y., Wu Y. H., Chiu D. T. 2004; Glucose-6-phosphate dehydrogenase-deficient cells show an increased propensity for oxidant-induced senescence. Free Radic Biol Med 36:580–591 [CrossRef]
    [Google Scholar]
  17. Denizot F., Lang R. 1986; Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 89:271–277 [CrossRef]
    [Google Scholar]
  18. Fujino G., Noguchi T., Takeda K., Ichijo H. 2006; Thioredoxin and protein kinases in redox signaling. Semin Cancer Biol 16:427–435 [CrossRef]
    [Google Scholar]
  19. Gil L., Martinez G., Gonzalez I., Tarinas A., Alvarez A., Giuliani A., Molina R., Tapanes R., Perez J., Leon O. S. 2003; Contribution to characterization of oxidative stress in HIV/AIDS patients. Pharmacol Res 47:217–224 [CrossRef]
    [Google Scholar]
  20. Hirasawa K., Kim A., Han H. S., Han J., Jun H. S., Yoon J. W. 2003; Effect of p38 mitogen-activated protein kinase on the replication of encephalomyocarditis virus. J Virol 77:5649–5656 [CrossRef]
    [Google Scholar]
  21. Ho M., Chen E. R., Hsu K. H., Twu S. J., Chen K. T., Tsai S. F., Wang J. R., Shih S. R. 1999; An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group. N Engl J Med 341:929–935 [CrossRef]
    [Google Scholar]
  22. Ho H. Y., Cheng M. L., Lu F. J., Chou Y. H., Stern A., Liang C. M., Chiu D. T. 2000; Enhanced oxidative stress and accelerated cellular senescence in glucose-6-phosphate dehydrogenase (G6PD)-deficient human fibroblasts. Free Radic Biol Med 29:156–169 [CrossRef]
    [Google Scholar]
  23. Ho H. Y., Cheng M. L., Chiu D. T. 2005; G6PD – an old bottle with new wine. Chang Gung Med J 28:606–612
    [Google Scholar]
  24. Ho H. Y., Wei T. T., Cheng M. L., Chiu D. T. 2006; Green tea polyphenol epigallocatechin-3-gallate protects cells against peroxynitrite-induced cytotoxicity: modulatory effect of cellular G6PD status. J Agric Food Chem 54:1638–1645 [CrossRef]
    [Google Scholar]
  25. Ho H. Y., Cheng M. L., Cheng P. F., Chiu D. T. 2007a; Low oxygen tension alleviates oxidative damage and delays cellular senescence in G6PD-deficient cells. Free Radic Res 41:571–579 [CrossRef]
    [Google Scholar]
  26. Ho H. Y., Cheng M. L., Chiu D. T. 2007b; Glucose-6-phosphate dehydrogenase – from oxidative stress to cellular functions and degenerative diseases. Redox Rep 12:109–118 [CrossRef]
    [Google Scholar]
  27. Huang C. C., Liu C. C., Chang Y. C., Chen C. Y., Wang S. T., Yeh T. F. 1999; Neurologic complications in children with enterovirus 71 infection. N Engl J Med 341:936–942 [CrossRef]
    [Google Scholar]
  28. Ishimaru Y., Nakano S., Yamaoka K., Takami S. 1980; Outbreaks of hand, foot, and mouth disease by enterovirus 71. High incidence of complication disorders of central nervous system. Arch Dis Child 55:583–588 [CrossRef]
    [Google Scholar]
  29. Ko W. S., Guo C. H., Yeh M. S., Lin L. Y., Hsu G. S., Chen P. C., Luo M. C., Lin C. Y. 2005; Blood micronutrient, oxidative stress, and viral load in patients with chronic hepatitis C. World J Gastroenterol 11:4697–4702
    [Google Scholar]
  30. Kyto V., Lapatto R., Lakkisto P., Saraste A., Voipio-Pulkki L. M., Vuorinen T., Pulkki K. 2004; Glutathione depletion and cardiomyocyte apoptosis in viral myocarditis. Eur J Clin Invest 34:167–175 [CrossRef]
    [Google Scholar]
  31. Lachgar A., Sojic N., Arbault S., Bruce D., Sarasin A., Amatore C., Bizzini B., Zagury D., Vuillaume M. 1999; Amplification of the inflammatory cellular redox state by human immunodeficiency virus type 1-immunosuppressive Tat and gp160 proteins. J Virol 73:1447–1452
    [Google Scholar]
  32. Lin T. Y., Chang L. Y., Hsia S. H., Huang Y. C., Chiu C. H., Hsueh C., Shih S. R., Liu C. C., Wu M. H. 2002; The 1998 enterovirus 71 outbreak in Taiwan: pathogenesis and management. Clin Infect Dis 34:Suppl. 2S52–S57 [CrossRef]
    [Google Scholar]
  33. Lin T. Y., Twu S. J., Ho M. S., Chang L. Y., Lee C. Y. 2003; Enterovirus 71 outbreaks, Taiwan: occurrence and recognition. Emerg Infect Dis 9:291–293 [CrossRef]
    [Google Scholar]
  34. Liu C. C., Tseng H. W., Wang S. M., Wang J. R., Su I. J. 2000; An outbreak of enterovirus 71 infection in Taiwan, 1998: epidemiologic and clinical manifestations. J Clin Virol 17:23–30 [CrossRef]
    [Google Scholar]
  35. Luo H., Yanagawa B., Zhang J., Luo Z., Zhang M., Esfandiarei M., Carthy C., Wilson J. E., Yang D., McManus B. M. 2002; Coxsackievirus B3 replication is reduced by inhibition of the extracellular signal-regulated kinase (ERK) signaling pathway. J Virol 76:3365–3373 [CrossRef]
    [Google Scholar]
  36. Luzzatto L., Battistuzzi G. 1985; Glucose-6-phosphate dehydrogenase. Adv Hum Genet 14:217–329. 386–388
    [Google Scholar]
  37. McMinn P. C. 2002; An overview of the evolution of enterovirus 71 and its clinical and public health significance. FEMS Microbiol Rev 26:91–107 [CrossRef]
    [Google Scholar]
  38. Oda T., Akaike T., Hamamoto T., Suzuki F., Hirano T., Maeda H. 1989; Oxygen radicals in influenza-induced pathogenesis and treatment with pyran polymer-conjugated SOD. Science 244:974–976 [CrossRef]
    [Google Scholar]
  39. Okuda M., Li K., Beard M. R., Showalter L. A., Scholle F., Lemon S. M., Weinman S. A. 2002; Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology 122:366–375 [CrossRef]
    [Google Scholar]
  40. Paradis V., Mathurin P., Kollinger M., Imbert-Bismut F., Charlotte F., Piton A., Opolon P., Holstege A., Poynard T., Bedossa P. 1997; In situ detection of lipid peroxidation in chronic hepatitis C: correlation with pathological features. J Clin Pathol 50:401–406 [CrossRef]
    [Google Scholar]
  41. Racaniello V. R. 2001; Picornaviridae : the viruses and their replication. In Fields Virology , 4th edn. pp 685–722Edited by Fields B. N., Knipe D. M., Howley P. M., Griffin. Philadelphia: Lippincott Williams & Wilkins;
    [Google Scholar]
  42. Royall J. A., Ischiropoulos H. 1993; Evaluation of 2′,7′-dichlorofluorescein and dihydrorhodamine 123 as fluorescent probes for intracellular H2O2 in cultured endothelial cells. Arch Biochem Biophys 302:348–355 [CrossRef]
    [Google Scholar]
  43. Schmidt N. J., Lennette E. H., Ho H. H. 1974; An apparently new enterovirus isolated from patients with disease of the central nervous system. J Infect Dis 129:304–309 [CrossRef]
    [Google Scholar]
  44. Schwarz K. B. 1996; Oxidative stress during viral infection: a review. Free Radic Biol Med 21:641–649 [CrossRef]
    [Google Scholar]
  45. Shih S. R., Tsai M. C., Tseng S. N., Won K. F., Shia K. S., Li W. T., Chern J. H., Chen G. W., Lee C. C. other authors 2004; Mutation in enterovirus 71 capsid protein VP1 confers resistance to the inhibitory effects of pyridyl imidazolidinone. Antimicrob Agents Chemother 48:3523–3529 [CrossRef]
    [Google Scholar]
  46. Takimoto S., Waldman E. A., Moreira R. C., Kok F., Pinheiro Fde P., Saes S. G., Hatch M., de Souza D. F., Carmona Rde C. other authors 1998; Enterovirus 71 infection and acute neurological disease among children in Brazil (1988–1990). Trans R Soc Trop Med Hyg 92:25–28 [CrossRef]
    [Google Scholar]
  47. Toborek M., Lee Y. W., Pu H., Malecki A., Flora G., Garrido R., Hennig B., Bauer H. C., Nath A. 2003; HIV-Tat protein induces oxidative and inflammatory pathways in brain endothelium. J Neurochem 84:169–179
    [Google Scholar]
  48. Torres M., Forman H. J. 2003; Redox signaling and the MAP kinase pathways. Biofactors 17:287–296 [CrossRef]
    [Google Scholar]
  49. Turchan J., Pocernich C. B., Gairola C., Chauhan A., Schifitto G., Butterfield D. A., Buch S., Narayan O., Sinai A. other authors 2003; Oxidative stress in HIV demented patients and protection ex vivo with novel antioxidants. Neurology 60:307–314 [CrossRef]
    [Google Scholar]
  50. Wan G. H., Tsai S. C., Chiu D. T. 2002; Decreased blood activity of glucose-6-phosphate dehydrogenase associates with increased risk for diabetes mellitus. Endocrine 19:191–195 [CrossRef]
    [Google Scholar]
  51. Wong W. R., Chen Y. Y., Yang S. M., Chen Y. L., Horng J. T. 2005; Phosphorylation of PI3K/Akt and MAPK/ERK in an early entry step of enterovirus 71. Life Sci 78:82–90 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.2008/001404-0
Loading
/content/journal/jgv/10.1099/vir.0.2008/001404-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error