1887

Abstract

The first 84 nt in the 3′ non-translated region (3′ NTR) of dengue type 1 virus (DENV-1) exhibit lower levels of conservation than the other regions; this region is named the variable region (VR). The VR is further divided into two subregions: a 5′-terminal hypervariable region (HVR) and a 3′-terminal semi-variable region (SVR). Recent reports suggested that the VR of DENV-2 is required for efficient virus growth in mammalian cells. To investigate whether this is also true for the VR of DENV-1, deletion or replacement mutations were introduced into the VR by using recombinant DENV-1 cDNA clones. Recombinant viruses with deletion of either or both subregions exhibited reduced growth properties compared with the original virus. Mutants with incompletely reversed or unrelated sequences in the HVR demonstrated growth properties similar to those of the original virus. However, a replacement mutation in the SVR did not cause recovery of growth properties. Furthermore, the amount of viral RNA was decreased in Vero cells infected with the growth-attenuated mutant viruses. Results of reporter translation assays suggest that VR mutations may not affect the translation process of DENV-1. These data indicate that the VR is important for DENV-1 replication and is associated with the accumulation of DENV-1 RNA in mammalian cells, and that the HVR and SVR in the VR may have different roles in DENV-1 replication.

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2007-08-01
2019-10-17
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References

  1. 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]
  2. Alvarez, D. E., Lodeiro, M. F., Luduena, 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]
  3. Bryant, J. E., Vasconcelos, P. F., Rijnbrand, R. C., Mutebi, J. P., Higgs, S. & Barrett, A. D. ( 2005; ). Size heterogeneity in the 3′ noncoding region of South American isolates of yellow fever virus. J Virol 79, 3807–3821.[CrossRef]
    [Google Scholar]
  4. 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]
  5. Edgil, D., Diamond, M. S., Holden, K. L., Paranjape, S. M. & Harris, E. ( 2003; ). Translation efficiency determines differences in cellular infection among dengue virus type 2 strains. Virology 317, 275–290.[CrossRef]
    [Google Scholar]
  6. Gritsun, T. S., Venugopal, K., Zanotto, P. M., Mikhailov, M. V., Sall, A. A., Holmes, E. C., Polkinghorne, I., Frolova, T. V., Pogodina, V. V. & other authors ( 1997; ). Complete sequence of two tick-borne flaviviruses isolated from Siberia and the UK: analysis and significance of the 5′ and 3′-UTRs. Virus Res 49, 27–39.[CrossRef]
    [Google Scholar]
  7. Gubler, D. J. ( 1998; ). Dengue and dengue hemorrhagic fever. Clin Microbiol Rev 11, 480–496.
    [Google Scholar]
  8. 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]
  9. Halstead, S. B. ( 1997; ). Epidemiology of dengue and dengue hemorrhagic fever. In Dengue and Dengue Hemorrhagic Fever, pp. 23–44. Edited by D. J. Gubler & G. Kuno. Wallingford, UK: CAB International.
  10. Holden, K. L. & Harris, E. ( 2004; ). Enhancement of dengue virus translation: role of the 3′ untranslated region and the terminal 3′ stem-loop domain. Virology 329, 119–133.[CrossRef]
    [Google Scholar]
  11. Khromykh, A. A. & Westaway, E. G. ( 1997; ). Subgenomic replicons of the flavivirus Kunjin: construction and applications. J Virol 71, 1497–1505.
    [Google Scholar]
  12. Khromykh, A. A., Meka, H., Guyatt, K. J. & Westaway, E. G. ( 2001; ). Essential role of cyclization sequences in flavivirus RNA replication. J Virol 75, 6719–6728.[CrossRef]
    [Google Scholar]
  13. Khromykh, A. A., Kondratieva, N., Sgro, J. Y., Palmenberg, A. & Westaway, E. G. ( 2003; ). Significance in replication of the terminal nucleotides of the flavivirus genome. J Virol 77, 10623–10629.[CrossRef]
    [Google Scholar]
  14. Kurane, I. & Ennis, F. A. ( 1997; ). Immunopathogenesis of dengue virus infections. In Dengue and Dengue Hemorrhagic Fever, pp. 273–294. Edited by D. J. Gubler & G. Kuno. Wallingford, UK: CAB International.
  15. Leitmeyer, K. C., Vaughn, D. W., Watts, D. M., Salas, R., Villalobos, I., de Ramos, C. & Rico-Hesse, R. ( 1999; ). Dengue virus structural differences that correlate with pathogenesis. J Virol 73, 4738–4747.
    [Google Scholar]
  16. Lindenbach, B. D. & Rice, C. M. ( 2001; ). Flaviviridae: the viruses and their replication. In Fields Virology, 4th edn, vol. 1, pp. 991–1041. Edited by D. M. Knipe & P. M. Howley. Philadelphia, PA: Lippincott Willams & Wilkins.
  17. Lo, M. K., Tilgner, M., Bernard, K. A. & Shi, P. Y. ( 2003; ). Functional analysis of mosquito-borne flavivirus conserved sequence elements within 3′ untranslated region of West Nile virus by use of a reporting replicon that differentiates between viral translation and RNA replication. J Virol 77, 10004–10014.[CrossRef]
    [Google Scholar]
  18. Ma, S. P., Yoshida, Y., Makino, Y., Tadano, M., Ono, T. & Ogawa, M. ( 2003; ). Short report: a major genotype of Japanese encephalitis virus currently circulating in Japan. Am J Trop Med Hyg 69, 151–154.
    [Google Scholar]
  19. Mandl, C. W., Holzmann, H., Meixner, T., Rauscher, S., Stadler, P. F., Allison, S. L. & Heinz, F. X. ( 1998; ). Spontaneous and engineered deletions in the 3′ noncoding region of tick-borne encephalitis virus: construction of highly attenuated mutants of a flavivirus. J Virol 72, 2132–2140.
    [Google Scholar]
  20. Markoff, L. ( 2004; ). 5′- and 3′-noncoding regions in flavivirus RNA. In The Flaviviruses: Structure, Replication, and Evolution, pp. 177–229. Edited by T. J. Chambers & T. P. Monath. Amsterdam: Elsevier.
  21. Men, R., Bray, M., Clark, D., Chanock, 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]
  22. Nam, J. H., Chae, S. L., Won, S. Y., Kim, E. J., Yoon, K. S., Kim, B. I., Jeong, Y. S. & Cho, H. W. ( 2001; ). Short report: genetic heterogeneity of Japanese encephalitis virus assessed via analysis of the full-length genome sequence of a Korean isolate. Am J Trop Med Hyg 65, 388–392.
    [Google Scholar]
  23. Nukui, Y., Tajima, S., Kotaki, A., Ito, M., Takasaki, T., Koike, K. & Kurane, I. ( 2006; ). Novel dengue virus type 1 from travelers to Yap State, Micronesia. Emerg Infect Dis 12, 343–346.[CrossRef]
    [Google Scholar]
  24. Proutski, V., Gould, E. A. & Holmes, E. C. ( 1997; ). Secondary structure of the 3′ untranslated region of flaviviruses: similarities and differences. Nucleic Acids Res 25, 1194–1202.[CrossRef]
    [Google Scholar]
  25. Rosen, L. ( 1977; ). The Emperor's New Clothes revisited, or reflections on the pathogenesis of dengue hemorrhagic fever. Am J Trop Med Hyg 26, 337–343.
    [Google Scholar]
  26. Shurtleff, A. C., Beasley, D. W., Chen, J. J., Ni, H., Suderman, M. T., Wang, H., Xu, R., Wang, E., Weaver, S. C. & other authors ( 2001; ). Genetic variation in the 3′ non-coding region of dengue viruses. Virology 281, 75–87.[CrossRef]
    [Google Scholar]
  27. Tajima, S., Zhuang, W. Z., Kato, M. V., Okada, K., Ikawa, Y. & Aida, Y. ( 1998; ). Function and conformation of wild-type p53 protein are influenced by mutations in bovine leukemia virus-induced B-cell lymphosarcoma. Virology 243, 735–746.
    [Google Scholar]
  28. Tajima, S., Nukui, Y., Ito, M., Takasaki, T. & Kurane, I. ( 2006; ). Nineteen nucleotides in the variable region of 3′ non-translated region are dispensable for the replication of dengue type 1 virus in vitro. Virus Res 116, 38–44.[CrossRef]
    [Google Scholar]
  29. Tilgner, M. & Shi, P. Y. ( 2004; ). Structure and function of the 3′ terminal six nucleotides of the West Nile virus genome in viral replication. J Virol 78, 8159–8171.[CrossRef]
    [Google Scholar]
  30. Tilgner, M., Deas, T. S. & Shi, P. Y. ( 2005; ). The flavivirus-conserved penta-nucleotide in the 3′ stem-loop of the West Nile virus genome requires a specific sequence and structure for RNA synthesis, but not for viral translation. Virology 331, 375–386.[CrossRef]
    [Google Scholar]
  31. Wang, E., Weaver, S. C., Shope, R. E., Tesh, R. B., Watts, D. M. & Barrett, A. D. ( 1996; ). Genetic variation in yellow fever virus: duplication in the 3′ noncoding region of strains from Africa. Virology 225, 274–281.[CrossRef]
    [Google Scholar]
  32. Yang, D. K., Kim, B. H., Kweon, C. H., Kwon, J. H., Lim, S. I. & Han, H. R. ( 2004; ). Molecular characterization of full-length genome of Japanese encephalitis virus (KV1899) isolated from pigs in Korea. J Vet Sci 5, 197–205.
    [Google Scholar]
  33. Zhou, Y., Mammem, M. P., Jr, Klungthong, C., Chinnawirotpisan, P., Vaughn, D. W., Nimmannitya, S., Kalayanarooj, S., Holmes, E. C. & Zhang, C. ( 2006; ). Comparative analysis reveals no consistent association between the secondary structure of the 3′-untranslated region of dengue viruses and disease syndrome. J Gen Virol 87, 2595–2603.[CrossRef]
    [Google Scholar]
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