1887

Abstract

Hepatitis G virus (HGV)/GB virus C (GBV-C) causes persistent, non-pathogenic infection in a large proportion of the human population. Epidemiological and genetic evidence indicates a long-term association between HGV/GBV-C and related viruses and a range of primate species, and the co-speciation of these viruses with their hosts during primate evolution. Using a combination of covariance scanning and analysis of variability at synonymous sites, we previously demonstrated that the coding regions of HGV/GBV-C may contain extensive secondary structure of undefined function (Simmonds & Smith, 73, 5787–5794, 1999 ). In this study we have carried out a detailed comparison of the structure of the 3′untranslated region (3′UTR) of HGV/GBV-C with that of the upstream NS5B coding sequence. By investigation of free energies on folding, secondary structure predictive algorithms and analysis of covariance between HGV/GBV-C genotypes 1–4 and the more distantly related HGV/GBV-C chimpanzee variant, we obtained evidence for extensive RNA secondary structure formation in both regions. In particular, the NS5B region contained long stem–loop structures of up to 38 internally paired nucleotides which were evolutionarily conserved between human and chimpanzee HGV/GBV-C variants. The prediction of similar structures in the same region of hepatitis C virus may allow the functions of these structures to be determined with a more tractable experimental model.

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2001-04-01
2020-01-24
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References

  1. Adams, N. J., Prescott, L. E., Jarvis, L. M., Lewis, J. C. M., McClure, M. O., Smith, D. B. & Simmonds, P. ( 1998; ). Detection of a novel flavivirus related to hepatitis G virus/GB virus C in chimpanzees. Journal of General Virology 79, 1871-1877.
    [Google Scholar]
  2. Birkenmeyer, L. G., Desai, S. M., Muerhoff, A. S., Leary, T. P., Simons, J. N., Montes, C. C. & Mushahwar, I. K. ( 1998; ). Isolation of a GB virus-related genome from a chimpanzee. Journal of Medical Virology 56, 44-51.[CrossRef]
    [Google Scholar]
  3. Blight, K. J. & Rice, C. M. ( 1997; ). Secondary structure determination of the conserved 98-base sequence at the 3′ terminus of hepatitis C virus genome RNA. Journal of Virology 71, 7345-7352.
    [Google Scholar]
  4. 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]
  5. Bukh, J. & Apgar, C. L. ( 1997; ). Five new or recently discovered (GBV-A) virus species are indigenous to New World monkeys and may constitute a separate genus of the Flaviviridae. Virology 229, 429-436.[CrossRef]
    [Google Scholar]
  6. Deng, R. T. & Brock, K. V. ( 1993; ). 5′ and 3′ untranslated regions of pestivirus genome – primary and secondary structure analyses. Nucleic Acids Research 21, 1949-1957.[CrossRef]
    [Google Scholar]
  7. Erker, J. C., Desai, S. M., Leary, T. P., Chalmers, M. L., Montes, C. C. & Mushahwar, I. K. ( 1998; ). Genomic analysis of two GB virus A variants isolated from captive monkeys. Journal of General Virology 79, 41-45.
    [Google Scholar]
  8. Gonzalez-Perez, M. A., Norder, H., Bergstrom, A., Lopez, E., Visona, K. A. & Magnius, L. O. ( 1997; ). High prevalence of GB virus C strains genetically related to strains with Asian origin in Nicaraguan hemophiliacs. Journal of Medical Virology 52, 149-155.[CrossRef]
    [Google Scholar]
  9. Goodfellow, I., Chaudhry, Y., Richardson, A., Meredith, J., Almond, J. W., Barclay, W. & Evans, D. J. ( 2000; ). Identification of a cis-acting replication element within the poliovirus coding region. Journal of Virology 74, 4590-4600.[CrossRef]
    [Google Scholar]
  10. Ito, T. & Lai, M. M. C. ( 1997; ). Determination of the secondary structure of and cellular protein binding to the 3′-untranslated region of the hepatitis C virus RNA genome. Journal of Virology 71, 8698-8706.
    [Google Scholar]
  11. Jarvis, L. M., Watson, H. G., McOmish, F., Peutherer, J. F., Ludlam, C. A. & Simmonds, P. ( 1994; ). Frequent reinfection and reactivation of hepatitis C virus genotypes in multitransfused hemophiliacs. Journal of Infectious Diseases 170, 1018-1022.[CrossRef]
    [Google Scholar]
  12. Katayama, Y., Apichartpiyakul, C., Handajani, R., Ishido, S. & Hotta, H. ( 1997; ). GB virus C hepatitis G virus (GBV-C/HGV) infection in Chiang Mai, Thailand, and identification of variants on the basis of 5′-untranslated region sequences. Archives of Virology 142, 2433-2445.[CrossRef]
    [Google Scholar]
  13. Katayama, K., Kageyama, T., Fukushi, S., Hoshino, F. B., Kurihara, C., Ishiyama, N., Okamura, H. & Oya, A. ( 1998; ). Full-length GBV-C/HGV genomes from nine Japanese isolates: characterization by comparative analyses. Archives of Virology 143, 1063-1075.[CrossRef]
    [Google Scholar]
  14. Kolykhalov, A. A., Feinstone, S. M. & Rice, C. M. ( 1996; ). Identification of a highly conserved sequence element at the 3′ terminus of hepatitis C virus genome RNA. Journal of Virology 70, 3363-3371.
    [Google Scholar]
  15. Leary, T. P., Muerhoff, A. S., Simons, J. N., Pilot-Matias, T. J., Erker, J. C., Chalmers, M. L., Schlauder, G. S., Dawson, G. J., Desai, S. M. & Mushahwar, I. K. ( 1996; ). Sequence and genomic organization of GBV-C: a novel member of the Flaviviridae associated with human non-A–E hepatitis. Journal of Medical Virology 48, 60-67.[CrossRef]
    [Google Scholar]
  16. Leary, T. P., Desai, S. M., Erker, J. C. & Mushahwar, I. K. ( 1997; ). The sequence and genomic organization of a GB virus A variant isolated from captive tamarins. Journal of General Virology 78, 2307-2313.
    [Google Scholar]
  17. Lefrere, J. J., Roudotthoraval, F., Morandjoubert, L., Brossard, Y., Parnetmathieu, F., Mariotti, M., Agis, F., Rouet, G., Lerable, J., Lefevre, G., Girot, R. & Loiseau, P. ( 1999; ). Prevalence of GB virus type C hepatitis G virus RNA and of anti-E2 in individuals at high or low risk for blood-borne or sexually transmitted viruses: evidence of sexual and parenteral transmission. Transfusion 39, 83-94.[CrossRef]
    [Google Scholar]
  18. Linnen, J., Wages, J., Zhangkeck, Z. Y., Fry, K. E., Krawczynski, K. Z., Alter, H., Koonin, E., Gallagher, M., Alter, M., Hadziyannis, S., Karayiannis, P., Fung, K., Nakatsuji, Y., Shih, J. W. K., Young, L., Piatak, M., Hoover, C., Fernandez, J., Chen, S., Zou, J. C., Morris, T., Hyams, K. C., Ismay, S., Lifson, J. D., Hess, G., Foung, S. K. H., Thomas, H., Bradley, D., Margolis, H. & Kim, J. P. ( 1996; ). Molecular cloning and disease association of hepatitis G virus: a transfusion-transmissible agent. Science 271, 505-508.[CrossRef]
    [Google Scholar]
  19. Lohmann, V., Korner, F., Koch, J. O., Herian, U., Theilmann, L. & Bartenschlager, R. ( 1999; ). Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 285, 110-113.[CrossRef]
    [Google Scholar]
  20. McKnight, K. L. & Lemon, S. M. ( 1998; ). The rhinovirus type 14 genome contains an internally located RNA structure that is required for viral replication. RNA 4, 1569-1584.[CrossRef]
    [Google Scholar]
  21. Muerhoff, A. S., Smith, D. B., Leary, T. P., Erker, J. C., Desai, S. M. & Mushahwar, I. K. ( 1997; ). Identification of GB virus C variants by phylogenetic analysis of 5′-untranslated and coding region sequences. Journal of Virology 71, 6501-6508.
    [Google Scholar]
  22. Nakao, H., Okamoto, H., Fukuda, M., Tsuda, F., Mitsui, T., Masuko, K., Lizuka, H., Miyakawa, Y. & Mayumi, M. ( 1997; ). Mutation rate of GB virus C hepatitis G virus over the entire genome and in subgenomic regions. Virology 233, 43-50.[CrossRef]
    [Google Scholar]
  23. Okamoto, H., Nakao, H., Inoue, T., Fukuda, M., Kishimoto, J., Iizuka, H., Tsuda, F., Miyakawa, Y. & Mayumi, M. ( 1997; ). The entire nucleotide sequences of two GB virus C/hepatitis G virus isolates of distinct genotypes from Japan. Journal of General Virology 78, 737-745.
    [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 Research 25, 1194-1202.[CrossRef]
    [Google Scholar]
  25. Rice, C. M., Lenches, E. M., Eddy, S. R., Shin, S. J., Sheets, R. L. & Strauss, J. H. ( 1985; ). Nucleotide sequence of yellow fever virus: implications for flavivirus gene expression and evolution. Science 229, 726-733.[CrossRef]
    [Google Scholar]
  26. Rijnbrand, R., Abell, G. & Lemon, S. M. ( 2000; ). Mutational analysis of the GB virus B internal ribosome entry site. Journal of Virology 74, 773-783.[CrossRef]
    [Google Scholar]
  27. Simmonds, P. & Smith, D. B. ( 1999; ). Structural constraints on RNA virus evolution. Journal of Virology 73, 5787-5794.
    [Google Scholar]
  28. Simons, J. N., Desai, S. M., Schultz, D. E., Lemon, S. M. & Mushahwar, I. K. ( 1996; ). Translation initiation in GB viruses A and C: evidence for internal ribosome entry and implications for genome organization. Journal of Virology 70, 6126-6135.
    [Google Scholar]
  29. Smith, D. B., Cuceanu, N., Davidson, F., Jarvis, L. M., Mokili, J. L. K., Hamid, S., Ludlam, C. A. & Simmonds, P. ( 1997; ). Discrimination of hepatitis G virus/GBV-C geographical variants by analysis of the 5′ non-coding region. Journal of General Virology 78, 1533-1542.
    [Google Scholar]
  30. Smith, D. B., Basaras, M., Frost, S., Haydon, D., Cuceanu, N., Prescott, L., Kamenka, C., Millband, D., Sathar, M. A. & Simmonds, P. ( 2000; ). Phylogenetic analysis of GBV-C/hepatitis G virus. Journal of General Virology 81, 769-780.
    [Google Scholar]
  31. Strauss, E. G. & Strauss, J. H. ( 1983; ). Replication strategies of the single stranded RNA viruses of eukaryotes. Current Topics in Microbiology and Immunology 105, 1-98.
    [Google Scholar]
  32. Tanaka, T., Kato, N., Cho, M. J., Sugiyama, K. & Shimotohno, K. ( 1996; ). Structure of the 3′ terminus of the hepatitis C virus genome. Journal of Virology 70, 3307-3312.
    [Google Scholar]
  33. Tanaka, Y., Mizokami, M., Orito, E., Ohba, K., Kato, T., Kondo, Y., Mboudjeka, I., Zekeng, L., Kaptue, L., Bikandou, B., Mpele, P., Takehisa, J., Hayami, M., Suzuki, Y. & Gojobori, T. ( 1998; ). African origin of GB virus C hepatitis G virus. FEBS Letters 423, 143-148.[CrossRef]
    [Google Scholar]
  34. Xiang, J., Wunschmann, S., Schmidt, W., Shao, J. & Stapleton, J. T. ( 2000; ). Full-length GB virus C (hepatitis G virus) RNA transcripts are infectious in primary CD4-positive T cells. Journal of Virology 74, 9125-9133.[CrossRef]
    [Google Scholar]
  35. Yu, H. Y., Grassmann, C. W. & Behrens, S. E. ( 1999; ). Sequence and structural elements at the 3′ terminus of bovine viral diarrhea virus genomic RNA: functional role during RNA replication. Journal of Virology 73, 3638-3648.
    [Google Scholar]
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