1887

Abstract

A comparative analysis was performed of the 3′-untranslated region (UTR) of (DENV) sampled from Bangkok, Thailand, over a 30 year period and representing all four serotypes. Considerable genetic variation was observed both within and among serotypes. Notably, a full-length version of the critical 3′-long stable hairpin structure was absent from some isolates, suggesting the occurrence of complex structural interactions within the 3′-UTR, including the influence of upstream mutations. The Thai sequences were then combined with 61 globally sampled isolates of DENV taken from patients with either dengue fever or severe dengue disease. No consistent association was found between 3′-UTR secondary structure and the clinical outcome of DENV infection, although some evidence for a trend in this direction was observed in DENV-2. It was concluded that the 3′-UTR is not the sole determinant of DENV virulence in nature, although variation in secondary structure may greatly influence viral fitness.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81994-0
2006-09-01
2019-11-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/9/2595.html?itemId=/content/journal/jgv/10.1099/vir.0.81994-0&mimeType=html&fmt=ahah

References

  1. Aaskov, J., Buzacott, K., Thu, H. M., Lowry, K. & Holmes, E. C. ( 2006; ). Long-term transmission of defective RNA viruses in humans and Aedes mosquitoes. Science 311, 236–238.[CrossRef]
    [Google Scholar]
  2. Alvarez, D. E., De Lella Ezcurra, A. L., Fucito, S. & Gamarnik, A. V. ( 2005a; ). Role of RNA structures present at the 3′UTR of dengue virus on translation, RNA synthesis, and viral replication. Virology 339, 200–212.[CrossRef]
    [Google Scholar]
  3. Alvarez, D. E., Lodeiro, M. F., Ludueña, S. J., Pietrasanta, L. I. & Gamarnik, A. V. ( 2005b; ). Long-range RNA-RNA interactions circularize the dengue virus genome. J Virol 79, 6631–6643.[CrossRef]
    [Google Scholar]
  4. Blackwell, J. L. & Brinton, M. A. ( 1995; ). BHK cell proteins that bind to the 39 stem-loop structure of the West Nile virus genome RNA. J Virol 69, 5650–5658.
    [Google Scholar]
  5. Chambers, T. J., Hahn, C. S., Galler, R. & Rice, C. M. ( 1990; ). Flavivirus genome organization, expression, and replication. Annu Rev Microbiol 44, 649–688.[CrossRef]
    [Google Scholar]
  6. Chiu, W. W., Kinney, R. M. & Dreher, T. W. ( 2005; ). Control of translation by the 5′- and 3′-terminal regions of the dengue virus genome. J Virol 79, 8303–8315.[CrossRef]
    [Google Scholar]
  7. Cologna, R. & Rico-Hesse, R. ( 2003; ). American genotype structures decrease dengue virus output from human monocytes and dendritic cells. J Virol 77, 3929–3938.[CrossRef]
    [Google Scholar]
  8. Durbin, A. P., Karron, R. A., Sun, W. & 10 other authors ( 2001; ). Attenuation and immunogenicity in humans of a live dengue virus type-4 vaccine candidate with a 30 nucleotide deletion in its 3′-untranslated region. Am J Trop Med Hyg 65, 405–413.
    [Google Scholar]
  9. Gubler, D. J. ( 2002; ). Epidemic dengue/dengue hemorrhagic fever as a public health, social and economic problem in the 21st century. Trends Microbiol 10, 100–103.[CrossRef]
    [Google Scholar]
  10. Hahn, C. S., Hahn, Y. S., Rice, C. M., Lee, E., Dalgarno, L., Strauss, E. G. & Strauss, J. H. ( 1987; ). Conserved elements in the 3′ untranslated region of flavivirus RNAs and potential cyclization sequences. J Mol Biol 198, 33–41.[CrossRef]
    [Google Scholar]
  11. Halstead, S. B., Porterfield, J. S. & O'Rourke, E. J. ( 1980; ). Enhancement of dengue virus infection in monocytes by flavivirus antisera. Am J Trop Med Hyg 29, 638–642.
    [Google Scholar]
  12. Hofacker, I. L., Fontana, W., Stadler, P. F., Bonhoeffer, S., Tacker, M. & Schuster, P. ( 1994; ). Fast folding and comparison of RNA secondary structures. Monatsh Chem 125, 167–188.[CrossRef]
    [Google Scholar]
  13. Klungthong, C., Zhang, C., Mammen, M. P., Jr, Ubol, S. & Holmes, E. C. ( 2004; ). The molecular epidemiology of dengue virus serotype 4 in Bangkok, Thailand. Virology 329, 168–179.[CrossRef]
    [Google Scholar]
  14. Leitmeyer, K. C., Vaughn, D. W., Watts, D. M., Salas, R., Villalobos de Chacon, I., Ramos, C. & Rico-Hesse, R. ( 1999; ). Dengue virus structural differences that correlate with pathogenesis. J Virol 73, 4738–4747.
    [Google Scholar]
  15. Lin, S. R., Hsieh, S. C., Yueh, Y. Y., Lin, T. H., Chao, D. Y., Chen, W. J., King, C. C. & Wang, W. K. ( 2004; ). Study of sequence variation of dengue type 3 virus in naturally infected mosquitoes and human hosts: implications for transmission and evolution. J Virol 78, 12717–12721.[CrossRef]
    [Google Scholar]
  16. Mangada, M. N. M. & Igarashi, A. ( 1997; ). Sequences of terminal non-coding regions from four dengue-2 viruses isolated from patients exhibiting different disease severities. Virus Genes 14, 5–12.[CrossRef]
    [Google Scholar]
  17. Mangada, M. N. M. & Igarashi, A. ( 1998; ). Molecular and in vitro analysis of eight dengue type 2 viruses isolated from patients exhibiting different disease severities. Virology 244, 458–466.[CrossRef]
    [Google Scholar]
  18. Mathews, D. H., Sabina, J., Zuker, M. & Turner, D. H. ( 1999; ). Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J Mol Biol 288, 911–940.[CrossRef]
    [Google Scholar]
  19. Men, R., Bray, M., Clark, D., Chanockm, R. M. & Lai, C. J. ( 1996; ). Dengue type 4 virus mutants containing deletions in the 3′ noncoding region of the RNA genome: analysis of growth restriction in cell culture and altered viremia pattern and immunogenicity in rhesus monkeys. J Virol 70, 3930–3937.
    [Google Scholar]
  20. Mongkolsapaya, J., Dejnirattisai, W., Xu, X.-N. & 11 other authors ( 2003; ). Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic fever. Nat Med 9, 921–927.[CrossRef]
    [Google Scholar]
  21. Nisalak, A., Endy, T. P., Nimmannitya, S. & 7 other authors ( 2003; ). Serotype-specific dengue virus circulation and dengue disease in Bangkok, Thailand from 1973 to 1999. Am J Trop Med Hyg 68, 191–202.
    [Google Scholar]
  22. Proutski, V., Gould, E. A. & Holmes, E. C. ( 1997a; ). Secondary structure of the 3′-untranslated region of flaviviruses: similarities and differences. Nucleic Acids Res 25, 1194–1202.[CrossRef]
    [Google Scholar]
  23. Proutski, V., Gaunt, M. W., Gould, E. A. & Holmes, E. C. ( 1997b; ). Secondary structure of the 3′-untranslated region of yellow fever virus: implications for virulence, attenuation and vaccine development. J Gen Virol 78, 1543–1549.
    [Google Scholar]
  24. Rauscher, S., Flamm, C., Mandl, C. W., Heinz, F. X. & Stadler, P. F. ( 1997; ). Secondary structure of the 3′-noncoding region of flavivirus genomes: comparative analysis of base pairing probabilities. RNA 3, 779–791.
    [Google Scholar]
  25. Rico-Hesse, R., Harrison, L. M., Salas, R. A. & 7 other authors ( 1997; ). Origins of dengue type 2 viruses associated with increased pathogenicity in the Americas. Virology 230, 244–251.[CrossRef]
    [Google Scholar]
  26. Rodriguez-Roche, R., Alvarez, M., Gritsun, T., Halstead, S., Kouri, G., Gould, E. A. & Guzman, M. G. ( 2005; ). Virus evolution during a severe dengue epidemic in Cuba, 1997. Virology 334, 154–159.[CrossRef]
    [Google Scholar]
  27. Shurtleff, A. C., Beasley, D. W. C., Chen, J. J. Y. & 9 other authors ( 2001; ). Genetic variation in the 3′ non-coding region of dengue viruses. Virology 281, 75–87.[CrossRef]
    [Google Scholar]
  28. Swofford, D. L. ( 2003; ). paup*. Phylogenetic analysis using parsimony (*and other methods). Version 4. Sunderland, MA: Sinauer Associates.
  29. Thompson, J. D., Gibson, T. J., Plewniak, F., Jeanmougin, F. & Higgins, D. G. ( 1997; ). The clustal_x windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25, 4876–4882.[CrossRef]
    [Google Scholar]
  30. Wang, W.-K., Lin, S. R., Lee, C.-M., King, C. C. & Chang, S.-C. ( 2002; ). Dengue type 3 virus in plasma is a population of closely related genomes: quasispecies. J Virol 76, 4662–4665.[CrossRef]
    [Google Scholar]
  31. Yu, L. & Markoff, L. ( 2005; ). The topology of bulges in the long stem of the flavivirus 3′ stem-loop is a major determinant of RNA replication competence. J Virol 79, 2309–2324.[CrossRef]
    [Google Scholar]
  32. Zeng, L., Falgout, B. & Markoff, L. ( 1998; ). Identification of specific nucleotide sequences within the conserved 3′-SL in the dengue type 2 virus genome required for replication. J Virol 72, 7510–7522.
    [Google Scholar]
  33. Zhang, C., Mammen, M. P., Jr, Chinnawirotpisan, P., Klungthong, C., Rodpradit, P., Monkongdee, P., Nimmannitya, S., Kalayanarooj, S. & Holmes, E. C. ( 2005; ). Clade replacements in dengue virus serotypes 1 and 3 are associated with changing serotype prevalence. J Virol 79, 15123–15130.[CrossRef]
    [Google Scholar]
  34. Zhang, C., Mammen, M. P., Jr, Chinnawirotpisan, P. & 7 other authors ( 2006; ). Structure and age of genetic diversity of dengue type-2 virus (DENV-2) in Thailand. J Gen Virol 87, 873–883.[CrossRef]
    [Google Scholar]
  35. Zuker, M. ( 2003; ). mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 31, 3406–3415.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81994-0
Loading
/content/journal/jgv/10.1099/vir.0.81994-0
Loading

Data & Media loading...

Supplements

[ Single PDF file] (164 KB)

PDF

[ Single PDF file] (118 KB)

PDF

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