1887

Abstract

Enterovirus 71 (EV71) is the causative agent of human diseases with distinct severity, from mild hand-foot-and-mouth disease to severe neurological syndromes, such as encephalitis and meningitis. Infection of several different cell lines with EV71 causes extensive cytopathic effect, leading to destruction of the entire monolayer and the death of infected cells. In this study, cell death processes during EV71 infection and the underlying mechanisms of them were investigated. The hallmarks of apoptosis, nuclear condensation and fragmentation, were observed 24 h after infection. Apoptosis in infected cells was also confirmed by detectable cleavage of cellular DNA and degradation of poly(ADP-ribose) polymerase. Transient expression of EV71 2A protease (2A) alone resulted in the induction of apoptotic change. Infection of EV71 or expression of EV71 2A leads to cleavage of the eukaryotic initiation factor 4GI, a key factor for host protein synthesis. This study added one more example to the growing list of human viruses that induce apoptosis by a virus-encoded protein.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-83-6-1367
2002-06-01
2024-04-24
Loading full text...

Full text loading...

/deliver/fulltext/jgv/83/6/0831367a.html?itemId=/content/journal/jgv/10.1099/0022-1317-83-6-1367&mimeType=html&fmt=ahah

References

  1. Agol V. I., Belov G. A., Bienz K., Egger D., Kolesnikova M. S., Raikhlin N. T., Romanova I. L., 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
    [Google Scholar]
  2. Agol V. I., Belov G. A., Bienz K., Egger D., Kolesnikova M. S., Romanova I. L., Sladkova L. V., Tolskaya E. A. 2000; Competing death programs in poliovirus-infected cells: commitment switch in the middle of the infectious cycle. Journal of Virology 74:5534–5541
    [Google Scholar]
  3. Aldabe R., Feduchi E., Novoa I., Carrasco L. 1995; Efficient cleavage of p220 by poliovirus 2Apro expression in mammalian cells: effects on vaccinia virus. Biochemical and Biophysical Research Communications 215:928–936
    [Google Scholar]
  4. Alexander J. P. Jr, Baden L., Pallansch M. A., Anderson L. J. 1994; Enterovirus 71 infections and neurologic disease-United States, 1977–1991. Journal of Infectious Diseases 169:905–908
    [Google Scholar]
  5. Ammendolia M. G., Tinari A., Calcabrini A., Superti F. 1999; Poliovirus infection induces apoptosis in CaCo-2 cells. Journal of Medical Virology 59:122–129
    [Google Scholar]
  6. Barco A., Feduchi E., Carrasco L. 2000; A stable HeLa cell line that inducibly expresses poliovirus 2Apro: effects on cellular and viral gene expression. Journal of Virology 74:2383–2392
    [Google Scholar]
  7. Bazan J. F., Fletterick R. J. 1988; Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications. Proceedings of the National Academy of Sciences, USA 85:7872–7876
    [Google Scholar]
  8. Belsham G. J., Sonenberg N. 1996; RNA–protein interactions in regulation of picornavirus RNA translation. Microbiological Reviews 60:499–511
    [Google Scholar]
  9. Borman A. M., Kirchweger R., Ziegler E., Rhoads R. E., Skern T., Kean K. M. 1997; eIF4G and its proteolytic cleavage products: effect on initiation of protein synthesis from capped, uncapped, and IRES-containing mRNAs. RNA 3:186–196
    [Google Scholar]
  10. Bovee M. L., Lamphear B. J., Rhoads R. E., Lloyd R. E. 1998; Direct cleavage of eIF4G by poliovirus 2A protease is inefficient in vitro . Virology 245:241–249
    [Google Scholar]
  11. Brown B. A., Pallansch M. A. 1995; Complete nucleotide sequence of enterovirus 71 is distinct from poliovirus. Virus Research 39:195–205
    [Google Scholar]
  12. Carthy C. M., Granville D. J., Watson K. A., Anderson D. R., Wilson J. E., Yang D., Hunt D. W., McManus B. M. 1998; Caspase activation and specific cleavage of substrates after coxsackievirus B3-induced cytopathic effect in HeLa cells. Journal of Virology 72:7669–7675
    [Google Scholar]
  13. Castelli J. C., Hassel B. A., Wood K. A., Li X. L., Amemiya K., Dalakas M. C., Torrence P. F., Youle R. J. 1997; A study of the interferon antiviral mechanism: apoptosis activation by the 2-5A system. Journal of Experimental Medicine 186:967–972
    [Google Scholar]
  14. Chang L.-Y., Huang Y.-C., Lin T.-Y. 1998; Fulminant neurogenic pulmonary oedema with hand, foot, and mouth disease. Lancet 352:367–368
    [Google Scholar]
  15. Chumakov M., Voroshilova M., Shindarov L., Lavrova I., Gracheva L., Koroleva G., Vasilenko S., Brodvarova I., Nikolova M., Gyurova S., Gacheva M., Mitov G., Ninov N., Tsylka E., Robinson I., Frolova M., Bashkirtsev V., Martiyanova L., Rodin V. 1979; Enterovirus 71 isolated from cases of epidemic poliomyelitis-like disease in Bulgaria. Archives of Virology 60:329–340
    [Google Scholar]
  16. Clemens M. J., Bushell M., Morley S. J. 1998; Degradation of eukaryotic polypeptide chain initiation factor (eIF) 4G in response to induction of apoptosis in human lymphoma cell lines. Oncogene 17:2921–2931
    [Google Scholar]
  17. Etchison D., Milburn S. C., Edery I., Sonenberg N., Hershey J. W. 1982; Inhibition of HeLa cell protein synthesis following poliovirus infection correlates with the proteolysis of a 220,000-dalton polypeptide associated with eucaryotic initiation factor 3 and a cap binding protein complex. Journal of Biological Chemistry 257:14806–14810
    [Google Scholar]
  18. Gilbert G. L., Dickson K. E., Waters M. J., Kennett M. L., Land S. A., Sneddon M. 1988; Outbreak of enterovirus 71 infection in Victoria, Australia, with a high incidence of neurologic involvement. Pediatric Infectious Disease Journal 7:484–488
    [Google Scholar]
  19. Girard S., Couderc T., Destombes J., Thiesson D., Delpeyroux F., Blondel B. 1999; Poliovirus induces apoptosis in the mouse central nervous system. Journal of Virology 73:6066–6072
    [Google Scholar]
  20. Goldstaub D., Gradi A., Bercovitch Z., Grosmann Z., Nophar Y., Luria S., Sonenberg N., Kahana C. 2000; Poliovirus 2A protease induces apoptotic cell death. Molecular and Cellular Biology 20:1271–1277
    [Google Scholar]
  21. Gradi A., Imataka H., Svitkin Y. V., Rom E., Raught B., Morino S., Sonenberg N. 1998; A novel functional human eukaryotic translation initiation factor 4G. Molecular and Cellular Biology 18:334–342
    [Google Scholar]
  22. Green D. R. 2000; Apoptotic pathways: paper wraps stone blunts scissors. Cell 102:1–4
    [Google Scholar]
  23. Haghighat A., Svitkin Y., Novoa I., Kuechler E., Skern T., Sonenberg N. 1996; The eIF4G–eIF4E complex is the target for direct cleavage by the rhinovirus 2A proteinase. Journal of Virology 70:8444–8450
    [Google Scholar]
  24. Hagiwara A., Tagaya I., Yoneyama T. 1978; Epidemic of hand, foot and mouth disease associated with enterovirus 71 infection. Intervirology 9:60–63
    [Google Scholar]
  25. Haller A. A., Semler B. L. 1995; Translation and host cell shutoff. In Human Enterovirus Infection pp 113–133 Edited by Rotbart Harley A. Washington, DC: ASM;
    [Google Scholar]
  26. Hayward J. C., Gillespie S. M., Kaplan K. M., Packer R., Pallansch M., Plotkin S., Schonberger L. B. 1989; Outbreak of poliomyelitis-like paralysis associated with enterovirus 71. Pediatric Infectious Disease Journal 8:611–616
    [Google Scholar]
  27. 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. Journal of Virology 74:4284–4290
    [Google Scholar]
  28. 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. New England Journal of Medicine 341:929–935
    [Google Scholar]
  29. Iizuka N., Kuge S., Nomoto A. 1987; Complete nucleotide sequence of the genome of coxsackievirus B1. Virology 156:64–73
    [Google Scholar]
  30. 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. Archives of Disease in Childhood 55:583–588
    [Google Scholar]
  31. Jackson R. J., Hunt S. L., Gibbs C. L., Kaminski A. 1994; Internal initiation of translation of picornavirus RNAs. Molecular Biology Reports 19:147–159
    [Google Scholar]
  32. Jelachich M. L., Lipton H. L. 1999; Restricted Theiler′s murine encephalomyelitis virus infection in murine macrophages induces apoptosis. Journal of General Virology 80:1701–1705
    [Google Scholar]
  33. Jenkins O., Booth J. D., Minor P. D., Almond J. W. 1987; The complete nucleotide sequence of coxsackievirus B4 and its comparison to other members of the Picornaviridae . Journal of General Virology 68:1835–1848
    [Google Scholar]
  34. Kaufmann S. H., Desnoyers S., Ottaviano Y., Davidson N. E., Poirier G. G. 1993; Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis. Cancer Research 53:3976–3985
    [Google Scholar]
  35. Kitamura N., Semler B. L., Rothberg P. G., Larsen G. R., Adler C. J., Dorner A. J., Emini E. A., Hanecak R., Lee J. J., van der Werf S., Anderson C. W., Wimmer E. 1981; Primary structure, gene organization and polypeptide expression of poliovirus RNA. Nature 291:547–553
    [Google Scholar]
  36. Krausslich H.-G., Nicklin M. J. H., Toyoda H., Etchison D., Wimmer E. 1987; Poliovirus proteinase 2A induces cleavage of the eucaryotic initiation factor 4F polyprotein p220. Journal of Virology 61:2711–2718
    [Google Scholar]
  37. Lamphear B. J., Yan R., Yang F., Waters D., Liebig H.-D., Klump H., Kuechler E., Skern T., Rhoads R. E. 1993; Mapping the cleavage site in protein synthesis initiation factor eIF-4γ of the 2A proteases from human coxsackievirus and rhinovirus. Journal of Biological Chemistry 268:19200–19203
    [Google Scholar]
  38. Lazebnik Y. A., Kaufmann S. H., Desnoyers S., Poirier G. G., Earnshaw W. C. 1994; Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature 371:346–347
    [Google Scholar]
  39. Lee S. B., Esteban M. 1994; The interferon-induced double-stranded RNA-activated protein kinase induces apoptosis. Virology 199:491–496
    [Google Scholar]
  40. Lee S. B., Rodriguez D., Rodriguez J. R., Esteban M. 1997; The apoptosis pathway triggered by the interferon-induced protein kinase PKR requires the third basic domain, initiates upstream of Bcl-2, and involves ICE-like proteases. Virology 231:81–88
    [Google Scholar]
  41. Liebig H.-D., Ziegler E., Yan R., Hartmuth K., Klump H., Kowalski H., Blaas D., Sommergruber W., Frasel L., Lamphear B., Rhoads R., Kuechler E., Skern T. 1993; Purification of two picornaviral 2A proteinases: interaction with eIF-4γ and influence on in vitro translation. Biochemistry 32:7581–7588
    [Google Scholar]
  42. Lindberg A. M., Stalhandske P. O., Pettersson U. 1987; Genome of coxsackievirus B3. Virology 156:50–63
    [Google Scholar]
  43. 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. Journal of Clinical Virology 17:23–30
    [Google Scholar]
  44. Lloyd R. E., Grubman M. J., Ehrenfeld E. 1988; Relationship of p220 cleavage during picornavirus infection to 2A proteinase sequencing. Journal of Virology 62:4216–4223
    [Google Scholar]
  45. López-Guerrero J. A., Alonso M., Martin-Belmonte F., Carrasco L. 2000; Poliovirus induces apoptosis in the human U937 promonocytic cell line. Virology 272:250–256
    [Google Scholar]
  46. Lum L. C. S., Wong K. T., Lam S. K., Chua K. B., Goh A. Y. T., Lim W. L., Ong B. B., Paul G., AbuBakar S., Lambert M. 1998; Fatal enterovirus 71 encephalomyelitis. Journal of Pediatrics 133:795–798
    [Google Scholar]
  47. Marissen W. E., Lloyd R. E. 1998; Eukaryotic translation initiation factor 4G is targeted for proteolytic cleavage by caspase 3 during inhibition of translation in apoptotic cells. Molecular and Cellular Biology 18:7565–7574
    [Google Scholar]
  48. Martin S. J., Green D. R., Cotter T. G. 1994; Dicing with death: dissecting the components of the apoptosis machinery. Trends in Biochemical Sciences 19:26–30
    [Google Scholar]
  49. Melcher A., Gough M., Todryk S., Vile R. 1999; Apoptosis or necrosis for tumor immunotherapy: what’s in a name?. Journal of Molecular Medicine 77:824–833
    [Google Scholar]
  50. Morley S. J., Curtis P. S., Pain V. M. 1997; eIF4G: translations mystery factor begins to yield its secrets. RNA 3:1085–1104
    [Google Scholar]
  51. Nagy G., Takatsy S., Kukan E., Mihaly I., Domok I. 1982; Virological diagnosis of enterovirus type 71 infections: experiences gained during an epidemic of acute CNS diseases in Hungary in 1978. Archives of Virology 71:217–227
    [Google Scholar]
  52. Oberhaus S. M., Smith R. L., Clayton G. H., Dermody T. S., Tyler K. L. 1997; Reovirus infection and tissue injury in the mouse central nervous system are associated with apoptosis. Journal of Virology 71:2100–2106
    [Google Scholar]
  53. O′Brien V. 1998; Viruses and apoptosis. Journal of General Virology 79:1833–1845
    [Google Scholar]
  54. Ohlmann T., Rau M., Pain V. M., Morley S. J. 1996; The C-terminal domain of eukaryotic protein synthesis initiation factor (eIF) 4G is sufficient to support cap-independent translation in the absence of eIF4E. EMBO Journal 15:1371–1382
    [Google Scholar]
  55. Pérez L., Carrasco L. 1992; Lack of direct correlation between p220 cleavage and the shut-off of host translation after poliovirus infection. Virology 189:178–186
    [Google Scholar]
  56. Roberts L. O., Seamons R. A., Belsham G. L. 1998; Recognition of picornavirus internal ribosome entry sites within cells; influence of cellular and viral proteins. RNA 4:520–529
    [Google Scholar]
  57. Roberts L. O., Boxall A. J., Lewis L. J., Belsham G. J., Kass G. E. N. 2000; Caspases are not involved in the cleavage of translation initiation factor eIF4GI during picornavirus infection. Journal of General Virology 81:1703–1707
    [Google Scholar]
  58. Roulston A., Marcellus R. C., Branton P. E. 1999; Virus and apoptosis. Annual Review of Microbiology 53:577–628
    [Google Scholar]
  59. Ryan M. D., Flint M. 1997; Virus-encoded proteinases of the picornavirus super-group. Journal of General Virology 78:699–723
    [Google Scholar]
  60. Sachs A. B., Sarnow P., Hentze M. W. 1997; Starting at the beginning, middle, and end: translation initiation in eukaryotes. Cell 89:831–838
    [Google Scholar]
  61. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: a Laboratory Manual , 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  62. Schmidt N. J., Lennette E. H., Ho H. H. 1974; An apparently new enterovirus isolated from patients with disease of the central nervous system. Journal of Infectious Diseases 129:304–309
    [Google Scholar]
  63. Shimizu H., Utama A., Yoshii K., Yoshida H., Yoneyama T., Sinniah M., Yusof M. A. B., Okuno Y., Okabe N., Shih S. R., Chen H. Y., Wang G. R., Kao C. L., Chang K. S. S., Miyamura T., Hagiwara A. 1999; Enterovirus 71 from fatal and nonfatal cases of hand, foot and mouth disease epidemics in Malaysia, Japan and Taiwan in 1997–1998. Japanese Journal of Infectious Diseases 52:12–15
    [Google Scholar]
  64. Skern T., Sommergruber W., Blaas D., Gruendler P., Fraundorfer F., Pieler C., Fogy I., Kuechler E. 1985; Human rhinovirus 2: complete nucleotide sequence and proteolytic processing signals in the capsid protein region. Nucleic Acids Research 13:2111–2126
    [Google Scholar]
  65. Sonenberg N., Gingras A. C. 1998; The mRNA 5′ cap-binding protein eIF4E and control of cell growth. Current Opinion in Cell Biology 10:268–275
    [Google Scholar]
  66. Stanway G., Hughes P. J., Mountford R. C., Minor P. D., Almond J. W. 1984; The complete nucleotide sequence of a common cold virus: human rhinovirus 14. Nucleic Acids Research 12:7859–7875
    [Google Scholar]
  67. Teodoro J. G., Branton P. E. 1997; Regulation of apoptosis by viral gene products. Journal of Virology 71:1739–1746
    [Google Scholar]
  68. Tolskaya E. A., Romanova L. I., Kolesnikova M. S., Ivannikova T. A., Smirnova E. A., Raikhlin N. T., Agol V. I. 1995; Apoptosis-inducing and apoptosis-preventing functions of poliovirus. Journal of Virology 69:1181–1189
    [Google Scholar]
  69. Tsunoda I., Kurtz C. I. B., Fujinami R. S. 1997; Apoptosis in acute and chronic central nervous system disease induced by Theiler′s murine encephalomyelitis virus. Virology 228:388–393
    [Google Scholar]
  70. Wang S. M., Liu C. C., Tseng H. W., Wang J. R., Huang C. C., Chen Y. J., Yang Y. J., Lin S. J., Yeh T. F. 1999; Clinical spectrum of enterovirus 71 infection in children in southern Taiwan, with an emphasis on neurological complications. Clinical Infectious Diseases 29:184–190
    [Google Scholar]
  71. Yu S. F., Lloyd R. E. 1991; Identification of essential amino acid residues in the functional activity of poliovirus 2A protease. Virology 182:615–625
    [Google Scholar]
  72. Yu S. F., Lloyd R. E. 1992; Characterization of the roles of conserved cysteine and histidine residues in poliovirus 2A protease. Virology 186:725–735
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-83-6-1367
Loading
/content/journal/jgv/10.1099/0022-1317-83-6-1367
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