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.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.83676-0
2008-07-01
2019-11-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/7/1622.html?itemId=/content/journal/jgv/10.1099/vir.0.83676-0&mimeType=html&fmt=ahah

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. 757–778. Edited by C. M. Fauquet, M. A. Mayo, J. Maniloff, U. Desselberger & L. A. Ball. San Diego: Elsevier Academic Press.
  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]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.83676-0
Loading
/content/journal/jgv/10.1099/vir.0.83676-0
Loading

Data & Media loading...

Most Cited This Month

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