1887

Abstract

Montana leukoencephalitis virus (MMLV), a virus isolated from bats, causes an encephalitis in small rodents reminiscent of flavivirus encephalitis in humans. The complete MMLV genome is 10690 nucleotides long and encodes a putative polyprotein of 3374 amino acids. The virus contains the same conserved motifs in genes that are believed to be interesting antiviral targets (NTPase/helicase, serine protease and RNA-dependent RNA polymerase) as flaviviruses of clinical importance. Phylogenetic analysis of the entire coding region has confirmed the classification of MMLV in the clade of the flaviviruses with no known vector (NKV) and within this clade to the Rio Bravo branch (both viruses have the bat as their vertebrate host). We have provided for the first time a comparative analysis of the RNA folding of the 3′ UTR of the NKV flaviviruses (Modoc, Rio Bravo and Apoi viruses, in addition to MMLV). Structural elements in the 3′ UTR that are preserved among other flaviviruses have been revealed, as well as elements that distinguish the NKV from the mosquito- and tick-borne flaviviruses. In particular, the pentanucleotide sequence 5′ CACAG 3′, which is conserved in all mosquito- and tick-borne flaviviruses, is replaced by the sequence 5′ C(C/U)(C/U)AG 3′ in the loop of the 3′ long stable hairpin structure of all four NKV flaviviruses. The availability of this latter sequence motif allows us to designate a virus as either an NKV or a vector-borne flavivirus.

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2002-08-01
2019-10-15
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References

  1. Bell, J. F. & Thomas, L. A. (1964). A new virus, ‘MML’, enzootic in bats (Myotis lucifungus) of Montana. American Journal of Tropical Medicine and Hygiene, 607–612.
  2. Billoir, F., De Chesse, R., Tolou, H., De Micco, P., Gould, E. A. & De Lamballerie, X. ( 2000; ). Phylogeny of the genus Flavivirus using complete coding sequences of arthropod-borne viruses and viruses with no known vector. Journal of General Virology 81, 781-790.
    [Google Scholar]
  3. Blackwell, J. L. & Brinton, M. A. ( 1995; ). BHK cell proteins that bind to the 3′ stem–loop structure of the West Nile virus genome RNA. Journal of Virology 69, 5650-5658.
    [Google Scholar]
  4. Blackwell, J. L. & Brinton, M. A. ( 1997; ). Translation elongation factor-1 alpha interacts with the 3′ stem–loop region of West Nile virus genomic RNA. Journal of Virology 71, 6433-6444.
    [Google Scholar]
  5. Brinton, M. A., Fernandez, A. V. & Dispoto, J. H. ( 1986; ). The 3′-nucleotides of flavivirus genomic RNA form a conserved secondary structure. Virology 153, 113-121.[CrossRef]
    [Google Scholar]
  6. Cammisa-Parks, H., Cisar, L. A., Kane, A. & Stollar, V. ( 1992; ). The complete nucleotide sequence of cell fusing agent (CFA): homology between the nonstructural proteins encoded by CFA and the nonstructural proteins encoded by arthropod-borne flaviviruses. Virology 189, 511-524.[CrossRef]
    [Google Scholar]
  7. Chambers, T. J., Hahn, C. S., Galler, R. & Rice, C. M. ( 1990; ). Flavivirus genome organization, expression, and replication. Annual Review of Microbiology 44, 649-688.[CrossRef]
    [Google Scholar]
  8. Charlier, N., Leyssen, P., Paeshuyse, J., Drosten, C., Schmitz, H., Van Lommel, A., De Clercq, E. & Neyts, J. ( 2002; ). Infection of SCID mice with Montana Myotis leukoencephalitis virus as a model for flavivirus encephalitis. Journal of General Virology 83, 1887-1896.
    [Google Scholar]
  9. Chen, C. J., Kuo, M. D., Chien, L. J., Hsu, S. L., Wang, Y. M. & Lin, J. H. ( 1997; ). RNA–protein interactions: involvement of NS3, NS5, and 3′ noncoding regions of Japanese encephalitis virus genomic RNA. Journal of Virology 71, 3466-3473.
    [Google Scholar]
  10. Grange, T., Bouloy, M. & Girard, M. ( 1985; ). Stable secondary structures at the 3′-end of the genome of yellow fever virus (17 D vaccine strain). FEBS Letters 188, 159-163.[CrossRef]
    [Google Scholar]
  11. 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., Lashkevich, V. A. & Gould, E. A. ( 1997; ). Complete sequence of two tick-borne flaviviruses isolated from Siberia and the UK: analysis and significance of the 5′ and 3′-UTRs. Virus Research 49, 27-39.[CrossRef]
    [Google Scholar]
  12. Gultyaev, A. P., Van-Batenburg, F. H. & Pleij, C. W. ( 1995; ). The computer simulation of RNA folding pathways using a genetic algorithm. Journal of Molecular Biology 250, 37-51.[CrossRef]
    [Google Scholar]
  13. 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. Journal of Molecular Biology 198, 33-41.[CrossRef]
    [Google Scholar]
  14. Han, L. L., Popovici, F., Alexander, J. J., Laurentia, V., Tengelsen, L. A., Cernescu, C., Gary, J. H., Ion, N. N., Campbell, G. L. & Tsai, T. F. ( 1999; ). Risk factors for West Nile virus infection and meningoencephalitis, Romania, 1996. Journal of Infectious Diseases 179, 230-233.[CrossRef]
    [Google Scholar]
  15. Heinz, F. X. & Mandl, C. W. ( 1993; ). The molecular biology of tick-borne encephalitis virus. Acta Pathologica, Microbiologica et Immunologica Scandinavica 101, 735-745.[CrossRef]
    [Google Scholar]
  16. Heinz, F. X., Collet, M. S., Purcell, R. H., Gould, E. A., Howard, C. R., Houghton, M., Moorman, R. J. M., Rice, C. M. & Thiel, H.-J. ( 2000; ). Flaviviridae. In Virus Taxonomy. Seventh Report of the International Committee for the Taxonomy of Viruses , pp. 859-878. Edited by M. H. V. Van Regenmortel, C. M. Fauquet, D. H. L. Bishop, E. B. Carstens, M. K. Estes, S. M. Lemon, J. Maniloff, M. A. Mayo, D. J. McGeoch, C. R. Pringle & R. B. Wickner. San Diego:Academic Press.
  17. Henikoff, S. & Henikoff, J. ( 1992; ). Amino acid substitution matrices for protein blocks. Proceedings of the National Academy of Sciences, USA 89, 10915-10919.[CrossRef]
    [Google Scholar]
  18. Kamer, G. & Argos, P. ( 1984; ). Primary structural comparison of RNA-dependent polymerases from plant, animal and bacterial viruses. Nucleic Acids Research 12, 7269-7282.[CrossRef]
    [Google Scholar]
  19. Khromykh, A. A., Meka, H., Guyatt, K. J. & Westaway, E. G. ( 2001; ). Essential role of cyclization sequences in flavivirus RNA replication. Journal of Virology 75, 6719-6728.[CrossRef]
    [Google Scholar]
  20. Koonin, E. V. ( 1993; ). Computer-assisted identification of a putative methyltransferase domain in NS5 protein of flaviviruses and lambda 2 protein of reovirus. Journal of General Virology 74, 733-740.[CrossRef]
    [Google Scholar]
  21. Kuno, G., Chang, G. J., Tsuchiya, K. R., Karabatsos, N. & Cropp, C. B. ( 1998; ). Phylogeny of the genus Flavivirus. Journal of Virology 72, 73-83.
    [Google Scholar]
  22. Leyssen, P., Charlier, N., Lemey, P., Billoir, F., Van Damme, A.-M., De Clercq, E., De Lamballerie, X. & Neyts, J. ( 2002; ). Complete genome sequence, taxonomic assignment, and comparative analysis of the untranslated regions of the Modoc virus, a flavivirus with no known vector. Virology 293, 125-140.[CrossRef]
    [Google Scholar]
  23. Maddison, W. P. & Maddison, D. R. ( 1989; ). Interactive analysis of phylogeny and character evolution using the computer program MacClade. Folia Primatologica 53, 190-202.[CrossRef]
    [Google Scholar]
  24. Mandl, C. W., Holzmann, H., Kunz, C. & Heinz, F. X. ( 1993; ). Complete genomic sequence of Powassan virus: evaluation of genetic elements in tick-borne versus mosquito-borne flaviviruses. Virology 194, 173-184.[CrossRef]
    [Google Scholar]
  25. 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. Journal of Virology 72, 2132-2140.
    [Google Scholar]
  26. Mangada, M. N. & 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]
  27. Mohan, P. M. & Padmanabhan, R. ( 1991; ). Detection of stable secondary structure at the 3′ terminus of dengue virus type 2 RNA. Gene 108, 185-191.[CrossRef]
    [Google Scholar]
  28. Monath, T. P. & Heinz, F. X. ( 1996; ). Flaviviruses. In Fields Virology , pp. 961-1034. Edited by B. N. Fields, D. M. Knipe & P. M. Howley. Philadelphia:Lippincott–Raven.
  29. Monath, W. R. & Lipman, D. J. ( 1988; ). Improved tools for biological sequence comparison. Proceedings of the National Academy of Sciences, USA 85, 2444-2448.[CrossRef]
    [Google Scholar]
  30. Pletnev, A. G., Yamshchikov, V. F. & Blinov, V. M. ( 1990; ). Nucleotide sequence of the genome and complete amino acid sequence of the polyprotein of tick-borne encephalitis virus. Virology 174, 250-263.[CrossRef]
    [Google Scholar]
  31. Poch, O., Sauvaget, I., Delarue, M. & Tordo, N. ( 1989; ). Identification of four conserved motifs among the RNA-dependent polymerase encoding elements. EMBO Journal 8, 3867-3874.
    [Google Scholar]
  32. Proutski, V., Gaunt, M. W., Gould, E. A. & Holmes, E. C. ( 1997a; ). Secondary structure of the 3′-untranslated region of yellow fever virus: implications for virulence, attenuation and vaccine development. Journal of General Virology 78, 1543-1549.
    [Google Scholar]
  33. Proutski, V., Gould, E. A. & Holmes, E. C. ( 1997b; ). Secondary structure of the 3′-untranslated region of flaviviruses: similarities and differences. Nucleic Acids Research 25, 1194-1202.[CrossRef]
    [Google Scholar]
  34. Proutski, V., Gristun, T. S., Gould, E. A. & Holmes, E. C. ( 1999; ). Biological consequences of deletions within the 3′ untranslated region of flaviviruses may be due to rearrangements of RNA secondary structure. Virus Research 64, 107-123.[CrossRef]
    [Google Scholar]
  35. Shi, P. Y., Brinton, M. A., Veal, J. M., Zhong, Y. Y. & Wilson, W. D. ( 1996; ). Evidence for the existence of a pseudoknot structure at the 3′ terminus of the flavivirus genomic RNA. Biochemistry 35, 4222-4230.[CrossRef]
    [Google Scholar]
  36. Shurtleff, A. C., Beasley, D. W., Chen, J. J., Ni, H., Suderman, M. T., Wang, H., Xu, R., Wang, E., Weaver, S. C., Watts, D. M., Russell, K. L. & Barrett, A. D. ( 2001; ). Genetic variation in the 3′ non-coding region of dengue viruses. Virology 281, 75-87.[CrossRef]
    [Google Scholar]
  37. Strimmer, K. & Von Haeseler, A. ( 1996; ). Quartet puzzling: a quartet maximum likelihood method for reconstructing tree topologies. Molecular Biology and Evolution 13, 964-969.[CrossRef]
    [Google Scholar]
  38. Von Heijne, G. ( 1984; ). How signal sequences maintain cleavage specificity. Journal of Molecular Biology 173, 243-251.[CrossRef]
    [Google Scholar]
  39. Wallner, G., Mandl, C. W., Kunz, C. & Heinz, F. X. ( 1995; ). The flavivirus 3′-noncoding region: extensive size heterogeneity independent of evolutionary relationships among strains of tick-borne encephalitis virus. Virology 213, 169-178.[CrossRef]
    [Google Scholar]
  40. Wengler, G. & Castle, E. ( 1986; ). Analysis of structural properties which possibly are characteristic for the 3′-terminal sequence of the genome RNA of flaviviruses. Journal of General Virology 67, 1183-1188.[CrossRef]
    [Google Scholar]
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