1887

Abstract

A mouse-adapted strain of human enterovirus 71 (HEV71) was selected by serial passage of a HEV71 clinical isolate (HEV71-26M) in Chinese hamster ovary (CHO) cells (CHO-26M) and in newborn BALB/c mice (MP-26M). Despite improved growth in CHO cells, CHO-26M did not show increased virulence in newborn BALB/c mice compared with HEV71-26M. By contrast, infection of newborn mice with MP-26M resulted in severe disease of high mortality. Skeletal muscle was the primary site of replication in mice for both viruses. However, MP-26M infection induced severe necrotizing myositis, whereas CHO-26M infection caused only mild inflammation. MP-26M was also isolated from whole blood, heart, liver, spleen and brain of infected mice. CHO-26M harboured a single mutation within the open reading frame (ORF), resulting in an amino acid substitution of K→I in the VP2 capsid protein; two further ORF mutations that resulted in amino acid substitutions were identified in MP-26M, located within the VP1 capsid protein (G→E) and the 2C protein (K→R). Infectious cDNA clone-derived mutant virus populations containing the mutations identified in CHO-26M and MP-26M were generated in order to study the molecular basis of CHO cell and mouse adaptation. The VP2 (K→I) change was responsible only for improved growth in CHO cells and did not lead to increased virulence in mice. Of the two amino acid substitutions identified in MP-26M, the VP1 (G→E) mutation alone was sufficient to increase virulence in mice to the level observed in MP-26M-infected mice.

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2008-07-01
2021-03-08
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References

  1. Arita M., Shimizu H., Nagata N., Ami Y., Suzaki Y., Sata T., Iwasaki T., Miyamura T. 2005; Temperature-sensitive mutants of enterovirus 71 show attenuation in cynomolgus monkeys. J Gen Virol 86:1391–1401 [CrossRef]
    [Google Scholar]
  2. Arita M., Ami Y., Wakita T., Shimizu H. 2008; Cooperative effect of the attenuation determinants derived from poliovirus Sabin 1 strain is essential for attenuation of enterovirus 71 in the NOD/SCID mouse infection model. J Virol 82:1787–1797 [CrossRef]
    [Google Scholar]
  3. Boyer J. C., Haenni A. L. 1994; Infectious transcripts and cDNA clones of RNA viruses. Virology 198:415–426 [CrossRef]
    [Google Scholar]
  4. Burke K. L., Almond J. W., Evans D. J. 1991; Antigen chimeras of poliovirus. Prog Med Virol 38:56–68
    [Google Scholar]
  5. Cardosa M. J., Perera D., Brown B. A., Cheon D. S., Chan H. M., Chan K. P., McMinn P. C. 2003; Molecular epidemiology of enterovirus 71 strains associated with recent outbreaks in the Asia–Pacific region: comparative analysis based on the VP1 and VP4 genes. Emerg Infect Dis 9:461–468 [CrossRef]
    [Google Scholar]
  6. Chen Y. C., Yu C. K., Wang Y. F., Liu C. C., Su I. J., Lei H. Y. 2004; A murine oral enterovirus 71 infection model with central nervous system involvement. J Gen Virol 85:69–77 [CrossRef]
    [Google Scholar]
  7. Chumakov M., Voroshilova M., Shindarov L., Lavrova I., Gracheva L., Koroleva G., Vasilenko S., Brodvarova I., Nikolova M. other authors 1979; Enterovirus 71 isolated from cases of epidemic poliomyelitis-like disease in Bulgaria. Arch Virol 60:329–340 [CrossRef]
    [Google Scholar]
  8. Colston E. M., Racaniello V. R. 1995; Poliovirus variants selected on mutant receptor-expressing cells identify capsid residues that expand receptor recognition. J Virol 69:4823–4829
    [Google Scholar]
  9. Couderc T., Hogle J., Le Blay H., Horaud F., Blondel B. 1993; Molecular characterization of mouse-virulent poliovirus type 1 Mahoney mutants: involvement of residues of polypeptides VP1 and VP2 located on the inner surface of the capsid protein shell. J Virol 67:3808–3817
    [Google Scholar]
  10. Couderc T., Guedo N., Calvez V., Pelletier I., Hogle J., Colbere-Garapin F., Blondel B. 1994; Substitutions in the capsid of poliovirus mutants selected in human neuroblastoma cells confer on the Mahoney type 1 strain a phenotype neurovirulent in mice. J Virol 68:8386–8391
    [Google Scholar]
  11. Couderc T., Delpeyroux F., Le Blay H., Blondel B. 1996; Mouse adaptation determinants of poliovirus type 1 enhance viral uncoating. J Virol 70:305–312
    [Google Scholar]
  12. Gualano R. C., Pryor M. J., Cauchi M. R., Wright P. J., Davidson A. D. 1998; Identification of a major determinant of mouse neurovirulence of dengue virus type 2 using stably cloned genomic-length cDNA. J Gen Virol 79:437–446
    [Google Scholar]
  13. Hashimoto I., Hagiwara A. 1982; Pathogenicity of a poliomyelitis-like disease in monkeys infected orally with enterovirus 71: a model for human infection. Neuropathol Appl Neurobiol 8:149–156 [CrossRef]
    [Google Scholar]
  14. Hashimoto I., Hagiwara A., Kodama H. 1978; Neurovirulence in cynomolgus monkeys of enterovirus 71 isolated from a patient with hand, foot and mouth disease. Arch Virol 56:257–261 [CrossRef]
    [Google Scholar]
  15. Hogle J. M., Chow M., Filman D. J. 1985; Three-dimensional structure of poliovirus at 2.9 Å resolution. Science 229:1358–1365 [CrossRef]
    [Google Scholar]
  16. Jia Q., Hogle J. M., Hashikawa T., Nomoto A. 2001; Molecular genetic analysis of revertants from a poliovirus mutant that is specifically adapted to the mouse spinal cord. J Virol 75:11766–11772 [CrossRef]
    [Google Scholar]
  17. Li J. P., Baltimore D. 1990; An intragenic revertant of a poliovirus 2C mutant has an uncoating defect. J Virol 64:1102–1107
    [Google Scholar]
  18. Lum L. C., Wong K. T., Lam S. K., Chua K. B., Goh A. Y., Lim W. L., Ong B. B., Paul G., AbuBakar S., Lambert M. 1998; Fatal enterovirus 71 encephalomyelitis. J Pediatr 133:795–798 [CrossRef]
    [Google Scholar]
  19. Martin A., Wychowski S., Couderc T., Crainic R., Hogle J., Girard M. 1988; Engineering a poliovirus type 2 antigenic site on a type 1 capsid results in a chimeric virus which is neurovirulent for mice. EMBO J 7:2839–2847
    [Google Scholar]
  20. Martin A., Benichou D., Couderc T., Hogle J., Wychowski S., Girard M. 1991; Use of a type 1/type 2 chimeric poliovirus to study determinants of poliovirus type 1 neurovirulence in a mouse model. Virology 180:648–658 [CrossRef]
    [Google Scholar]
  21. 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]
  22. McMinn P., Stratov I., Nagarajan L., Davis S. 2001a; Neurological manifestations of enterovirus 71 infection in children during an outbreak of hand, foot, and mouth disease in Western Australia. Clin Infect Dis 32:236–242 [CrossRef]
    [Google Scholar]
  23. McMinn P. C., Lindsay K., Perera D., Chan H. M., Chan K. P., Cardosa M. J. 2001b; Phylogenetic analysis of enterovirus 71 strains isolated during linked epidemics in Malaysia, Singapore and Western Australia. J Virol 75:7732–7738 [CrossRef]
    [Google Scholar]
  24. Pfister T., Wimmer E. 1999; Characterization of the nucleoside triphosphatase activity of poliovirus protein 2C reveals a mechanism by which guanidine inhibits poliovirus replication. J Biol Chem 274:6992–7001 [CrossRef]
    [Google Scholar]
  25. Reed L. J., Muench H. 1938; A simple method of estimating fifty percent endpoints. Am J Hyg 27:493–497
    [Google Scholar]
  26. 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]
  27. Stanway G., Brown F., Christian P., Hovi T., Hyypiä T., King A. M. Q., Knowles N. J., Lemon S. M., Minor P. D. other authors 2005; Family Picornaviridae . In Virus Taxonomy. Eighth Report of the International Committee on Taxonomy of Viruses pp 757–778Edited by Fauquet C. M., Mayo M. A., Maniloff J., Desselberger U., Ball. San Diego: Elsevier Academic Press;
    [Google Scholar]
  28. Teterina N. L., Egger D., Bienz K., Brown D. M., Semler B. L., Ehrenfeld E. 2001; Requirements for assembly of poliovirus replication complexes and negative-strand RNA synthesis. J Virol 75:3841–3850 [CrossRef]
    [Google Scholar]
  29. Vance L. M., Moscufo N., Chow M., Heinz B. A. 1997; Poliovirus 2C region functions during encapsidation of viral RNA. J Virol 71:8759–8765
    [Google Scholar]
  30. Wang Y. F., Chou C. T., Lei H. Y., Liu C. C., Wang S. M., Yan J. J., Su I. J., Wang J. R., Yeh T. M. other authors 2004; A mouse-adapted enterovirus 71 strain causes neurological disease in mice after oral infection. J Virol 78:7916–7924 [CrossRef]
    [Google Scholar]
  31. Wien M. W., Curry S., Filman D. J., Hogle J. M. 1997; Structural studies of poliovirus mutants that overcome receptor defects. Nat Struct Biol 4:666–674 [CrossRef]
    [Google Scholar]
  32. Wright A. J., Phillpotts R. J. 1998; Humane endpoints are an objective measure of morbidity in Venezuelan encephalomyelitis virus infection of mice. Arch Virol 143:1155–1162 [CrossRef]
    [Google Scholar]
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