1887

Journal of General Virology header logo

Volume 93, Issue 11

Specific cell tropism and neutralization of human parechovirus types 1 and 3: implications for pathogenesis and therapy development Free

Abstract

Human parechoviruses (HPeVs) are picornaviruses frequently infecting humans. While HPeV1 is associated with mild disease, HPeV3 is the cause of neonatal sepsis and meningitis. To test whether replication kinetics of HPeV1 and HPeV3 could be related to pathogenicity, HPeV1 and HPeV3 strains isolated from patients were cultured on cell lines of gastrointestinal, respiratory and neural origin, and replication kinetics were measured by real-time PCR. No relationship was found between clinical symptoms and replication of the HPeV1 strains. In contrast, the HPeV3 strains showed faster replication in neural cells and there was a relationship between higher replication kinetics and neuropathogenicity in the patient. Furthermore, HPeV1 could be neutralized efficiently by its specific antibody and by intravenous immunoglobulins (IVIG), while most HPeV3 strains could not be neutralized. In IVIG, very low neutralizing antibody (nAb) titres against HPeV3 were found. Additionally, very low nAb titres were observed in sera of two HPeV3-infected donors, while high nAb titres against HPeV1 could be detected. Our data suggest that the mild clinical course of HPeV1 infection is primarily influenced by strong nAb responses, while HPeV3 might be difficult to neutralize and therefore the course of infection will mainly be determined by cell tropism.

  • Received:
  • Accepted:
  • Published Online:
© 2012 SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.043323-0
2012-11-01
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/93/11/2363.html?itemId=/content/journal/jgv/10.1099/vir.0.043323-0&mimeType=html&fmt=ahah

References

  1. Abzug M. J., Keyserling H. L., Lee M. L., Levin M. J., Rotbart H. A. 1995; Neonatal enterovirus infection: virology, serology, and effects of intravenous immune globulin. Clin Infect Dis 20:1201–1206 [View Article][PubMed]
     [Google Scholar]
  2. Al-Sunaidi M., Williams C. H., Hughes P. J., Schnurr D. P., Stanway G. 2007; Analysis of a new human parechovirus allows the definition of parechovirus types and the identification of RNA structural domains. J Virol 81:1013–1021 [View Article][PubMed]
     [Google Scholar]
  3. Alho A., Marttila J., Ilonen J., Hyypiä T. 2003; Diagnostic potential of parechovirus capsid proteins. J Clin Microbiol 41:2294–2299 [View Article][PubMed]
     [Google Scholar]
  4. Benschop K. S., Schinkel J., Minnaar R. P., Pajkrt D., Spanjerberg L., Kraakman H. C., Berkhout B., Zaaijer H. L., Beld M. G., Wolthers K. C. 2006a; Human parechovirus infections in Dutch children and the association between serotype and disease severity. Clin Infect Dis 42:204–210 [View Article][PubMed]
     [Google Scholar]
  5. Benschop K. S. M., Schinkel J., Luken M. E., van den Broek P. J. M., Beersma M. F. C., Menelik N., van Eijk H. W. M., Zaaijer H. L., VandenBroucke-Grauls C. M. J. E.other authors 2006b; Fourth human parechovirus serotype. Emerg Infect Dis 12:1572–1575 [View Article][PubMed]
     [Google Scholar]
  6. Benschop K., Molenkamp R., van der Ham A., Wolthers K., Beld M. 2008a; Rapid detection of human parechoviruses in clinical samples by real-time PCR. J Clin Virol 41:69–74 [View Article][PubMed]
     [Google Scholar]
  7. Benschop K., Thomas X., Serpenti C., Molenkamp R., Wolthers K. 2008b; High prevalence of human parechovirus (HPeV) genotypes in the Amsterdam region and identification of specific HPeV variants by direct genotyping of stool samples. J Clin Microbiol 46:3965–3970 [View Article][PubMed]
     [Google Scholar]
  8. Benschop K. S., Williams C. H., Wolthers K. C., Stanway G., Simmonds P. 2008c; Widespread recombination within human parechoviruses: analysis of temporal dynamics and constraints. J Gen Virol 89:1030–1035 [View Article][PubMed]
     [Google Scholar]
  9. Benschop K., Minnaar R., Koen G., van Eijk H., Dijkman K., Westerhuis B., Molenkamp R., Wolthers K. 2010a; Detection of human enterovirus and human parechovirus (HPeV) genotypes from clinical stool samples: polymerase chain reaction and direct molecular typing, culture characteristics, and serotyping. Diagn Microbiol Infect Dis 68:166–173 [View Article][PubMed]
     [Google Scholar]
  10. Benschop K. S., de Vries M., Minnaar R. P., Stanway G., van der Hoek L., Wolthers K. C., Simmonds P. 2010b; Comprehensive full-length sequence analyses of human parechoviruses: diversity and recombination. J Gen Virol 91:145–154 [View Article][PubMed]
     [Google Scholar]
  11. Boivin G., Abed Y., Boucher F. D. 2005; Human parechovirus 3 and neonatal infections. Emerg Infect Dis 11:103–105 [View Article][PubMed]
     [Google Scholar]
  12. Boonyakiat Y., Hughes P. J., Ghazi F., Stanway G. 2001; Arginine-glycine-aspartic acid motif is critical for human parechovirus 1 entry. J Virol 75:10000–10004 [View Article][PubMed]
     [Google Scholar]
  13. Drexler J. F., Grywna K., Stöcker A., Almeida P. S., Medrado-Ribeiro T. C., Eschbach-Bludau M., Petersen N., da Costa-Ribeiro-Jr H., Drosten C. 2009; Novel human parechovirus from Brazil. Emerg Infect Dis 15:310–313 [View Article][PubMed]
     [Google Scholar]
  14. Engle M. J., Goetz G. S., Alpers D. H. 1998; Caco-2 cells express a combination of colonocyte and enterocyte phenotypes. J Cell Physiol 174:362–369 [View Article][PubMed]
     [Google Scholar]
  15. Harvala H., Robertson I., Chieochansin T., McWilliam Leitch E. C., Templeton K., Simmonds P. 2009; Specific association of human parechovirus type 3 with sepsis and fever in young infants, as identified by direct typing of cerebrospinal fluid samples. J Infect Dis 199:1753–1760 [View Article][PubMed]
     [Google Scholar]
  16. Harvala H., Wolthers K. C., Simmonds P. 2010; Parechoviruses in children: understanding a new infection. Curr Opin Infect Dis 23:224–230 [View Article][PubMed]
     [Google Scholar]
  17. Ito M., Yamashita T., Tsuzuki H., Takeda N., Sakae K. 2004; Isolation and identification of a novel human parechovirus. J Gen Virol 85:391–398 [View Article][PubMed]
     [Google Scholar]
  18. Joki-Korpela P., Hyypiä T. 1998; Diagnosis and epidemiology of echovirus 22 infections. Clin Infect Dis 27:129–136 [View Article][PubMed]
     [Google Scholar]
  19. Joki-Korpela P., Roivainen M., Lankinen H., Pöyry T., Hyypiä T. 2000; Antigenic properties of human parechovirus 1. J Gen Virol 81:1709–1718[PubMed]
     [Google Scholar]
  20. Joki-Korpela P., Marjomäki V., Krogerus C., Heino J., Hyypiä T. 2001; Entry of human parechovirus 1. J Virol 75:1958–1967 [View Article][PubMed]
     [Google Scholar]
  21. Kung C. M., King C. C., Lee C. N., Huang L. M., Lee P. I., Kao C. L. 2007; Differences in replication capacity between enterovirus 71 isolates obtained from patients with encephalitis and those obtained from patients with herpangina in Taiwan. J Med Virol 79:60–68 [View Article][PubMed]
     [Google Scholar]
  22. Lévy P., Robin H., Kornprobst M., Capeau J., Cherqui G. 1998; Enterocytic differentiation of the human Caco-2 cell line correlates with alterations in integrin signaling. J Cell Physiol 177:618–627 [View Article][PubMed]
     [Google Scholar]
  23. Li L., Victoria J., Kapoor A., Naeem A., Shaukat S., Sharif S., Alam M. M., Angez M., Zaidi S. Z., Delwart E. 2009; Genomic characterization of novel human parechovirus type. Emerg Infect Dis 15:288–291 [View Article][PubMed]
     [Google Scholar]
  24. Pajkrt D., Benschop K. S., Westerhuis B., Molenkamp R., Spanjerberg L., Wolthers K. C. 2009; Clinical characteristics of human parechoviruses 4–6 infections in young children. Pediatr Infect Dis J 28:1008–1010 [View Article][PubMed]
     [Google Scholar]
  25. Reed L. J., Muench H. 1938; A simple method of estimating fifty per cent endpoints. Am J Epidemiol 27:493–497
     [Google Scholar]
  26. Tauriainen S., Martiskainen M., Oikarinen S., Lönnrot M., Viskari H., Ilonen J., Simell O., Knip M., Hyöty H. 2007; Human parechovirus 1 infections in young children – no association with type 1 diabetes. J Med Virol 79:457–462 [View Article][PubMed]
     [Google Scholar]
  27. Triantafilou K., Triantafilou M., Takada Y., Fernandez N. 2000; Human parechovirus 1 utilizes integrins αvβ3 and αvβ1 as receptors. J Virol 74:5856–5862 [View Article][PubMed]
     [Google Scholar]
  28. van der Sanden S., de Bruin E., Vennema H., Swanink C., Koopmans M., van der Avoort H. 2008; Prevalence of human parechovirus in the Netherlands in 2000 to 2007. J Clin Microbiol 46:2884–2889 [View Article][PubMed]
     [Google Scholar]
  29. Verboon-Maciolek M. A., Krediet T. G., Gerards L. J., de Vries L. S., Groenendaal F., van Loon A. M. 2008; Severe neonatal parechovirus infection and similarity with enterovirus infection. Pediatr Infect Dis J 27:241–245 [View Article][PubMed]
     [Google Scholar]
  30. Verdaguer N., Mateu M. G., Andreu D., Giralt E., Domingo E., Fita I. 1995; Structure of the major antigenic loop of foot-and-mouth disease virus complexed with a neutralizing antibody: direct involvement of the Arg-Gly-Asp motif in the interaction. EMBO J 14:1690–1696[PubMed]
     [Google Scholar]
  31. Watanabe K., Oie M., Higuchi M., Nishikawa M., Fujii M. 2007; Isolation and characterization of novel human parechovirus from clinical samples. Emerg Infect Dis 13:889–895 [View Article][PubMed]
     [Google Scholar]
  32. Wen Y. Y., Chang T. Y., Chen S. T., Li C., Liu H. S. 2003; Comparative study of enterovirus 71 infection of human cell lines. J Med Virol 70:109–118 [View Article][PubMed]
     [Google Scholar]
  33. Wigand R., Sabin A. B. 1961; Properties of ECHO types 22, 23 and 24 viruses. Arch Gesamte Virusforsch 11:224–247 [View Article][PubMed]
     [Google Scholar]
  34. Wildenbeest J. G., Harvala H., Pajkrt D., Wolthers K. C. 2010; The need for treatment against human parechoviruses: how, why and when?. Expert Rev Anti Infect Ther 8:1417–1429 [View Article][PubMed]
     [Google Scholar]
  35. Wolthers K. C., Benschop K. S., Schinkel J., Molenkamp R., Bergevoet R. M., Spijkerman I. J., Kraakman H. C., Pajkrt D. 2008; Human parechoviruses as an important viral cause of sepsislike illness and meningitis in young children. Clin Infect Dis 47:358–363 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.043323-0
Loading
Specific cell tropism and neutralization of human parechovirus types 1 and 3: implications for pathogenesis and therapy development
J. Gen. Virol. 93, 2363 (2012); https://doi.org/10.1099/vir.0.043323-0
/content/journal/jgv/10.1099/vir.0.043323-0
/content/journal/jgv/10.1099/vir.0.043323-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

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