1887

Abstract

We determined the sequence of the hepatitis delta virus (HDV) genome in 40 Japanese patients, most of whom were from the Miyako Islands, Okinawa, Japan. Consensus sequences from 33 HDV full genomes out of a total of 40 patients were determined by directly sequencing four partially overlapping PCR products. Phylogenetic tree analysis classified these 33 complete HDV genomes as HDV genotype I (two patients), genotype IIa (one patient) and genotype IIb (30 patients). Among the 30 genotype IIb patients, there were two clusters of genetic variants. One group consisted of six isolates showing significant homology with genotype IIb, previously reported from Taiwan. The other group consisted of 24 isolates, whose sequences formed a new genetic subgroup (genotype IIb-Miyako; IIb-M). When the genetic structures were compared in detail between IIb and IIb-M, characteristic variations were found in the C-terminal sequence of the large delta antigen-conferring packaging signal as well as the RNA editing site. Determination of subclasses of genotype IIb in a total of 37 patients, including seven HDV patients whose partial HDV sequence was determined, revealed eight patients with IIb and 29 patients with IIb-M. Although there was no significant difference in the clinical background or virological state of hepatitis B virus between these two groups, patients with genotype IIb-M showed greater progression of chronic hepatitis and cirrhosis than those with genotype IIb (=0·0009). These data indicate the existence of a genetic subgroup of HDV genotype IIb, which is associated with different clinical characteristics and which could be related to genetic variations in functionally important parts of the HDV genome.

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2003-12-01
2019-10-15
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References

  1. Arakawa, Y., Moriyama, M., Taira, M., Hayashi, N., Tanaka, N., Okubo, H. & Sugitani, M. ( 2000; ). Molecular analysis of hepatitis D virus infection in Miyako Island, a small Japanese island. J Viral Hepat 7, 375–381.[CrossRef]
    [Google Scholar]
  2. Casey, J. L. ( 2002; ). RNA editing in hepatitis delta virus genotype III requires a branched double-hairpin RNA structure. J Virol 76, 7385–7397.[CrossRef]
    [Google Scholar]
  3. Casey, J. L., Bergmann, K. F., Brown, T. L. & Gerin, J. L. ( 1992; ). Structural requirements for RNA editing in hepatitis delta virus: evidence for a uridine-to-cytidine editing mechanism. Proc Natl Acad Sci U S A 89, 7149–7153.[CrossRef]
    [Google Scholar]
  4. Casey, J. L., Brown, T. L., Colan, E. J., Wignall, F. S. & Gerin, J. L. ( 1993; ). A genotype of hepatitis D virus that occurs in northern South America. Proc Natl Acad Sci U S A 90, 9016–9020.[CrossRef]
    [Google Scholar]
  5. Chang, M. F., Sun, C. Y., Chen, C. J. & Chang, S. C. ( 1993; ). Functional motifs of delta antigen essential for RNA binding and replication of hepatitis delta virus. J Virol 67, 2529–2536.
    [Google Scholar]
  6. Chen, P. J., Chang, F. L., Wang, C. J., Lin, C. J., Sung, S. Y. & Chen, D. S. ( 1992; ). Functional study of hepatitis delta virus large antigen in packaging and replication inhibition: role of the amino-terminal leucine zipper. J Virol 66, 2853–2859.
    [Google Scholar]
  7. Chomczynski, P. & Sacchi, N. ( 1987; ). Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction. Anal Biochem 162, 156–159.
    [Google Scholar]
  8. Enomoto, N., Kurosaki, M., Tanaka, Y., Marumo, F. & Sato, C. ( 1994; ). Fluctuation of hepatitis C virus quasispecies in persistent infection and interferon treatment revealed by single-strand conformation polymorphism analysis. J Gen Virol 75, 1361–1369.[CrossRef]
    [Google Scholar]
  9. Gerin, J. L., Casey, J. L. & Purcell, R. H. ( 2002; ). Hepatitis delta virus. In Viral Hepatitis, pp. 169–182. Edited by F. Blaine Hollinger. Philadelphia: Lippincott Williams & Wilkins.
  10. Glenn, J. S., Watson, J. A., Havel, C. M. & White, J. M. ( 1992; ). Identification of a prenylation site in delta virus large antigen. Science 256, 1331–1333.[CrossRef]
    [Google Scholar]
  11. Hsu, S. C., Syu, W. J., Sheen, I. J., Liu, H. T., Jeng, K. S. & Wu, J. C. ( 2002; ). Varied assembly and RNA editing efficiencies between genotypes I and II hepatitis D virus and their implications. Hepatology 35, 665–672.[CrossRef]
    [Google Scholar]
  12. Imazeki, F., Omata, M. & Ohto, M. ( 1991; ). Complete nucleotide sequence of hepatitis delta virus RNA in Japan. Nucleic Acids Res 19, 5439.[CrossRef]
    [Google Scholar]
  13. Ivaniushina, V., Radjef, N., Alexeeva, M., Gault, E., Semenov, S., Salhi, M., Kiselev, O. & Deny, P. ( 2001; ). Hepatitis delta virus genotypes I and II cocirculate in an endemic area of Yakutia, Russia. J Gen Virol 82, 2709–2718.
    [Google Scholar]
  14. Kamisango, K., Kamogawa, C., Sumi, M., Goto, S., Hirao, A., Gonzales, F., Yasuda, K. & Iino, S. ( 1999; ). Quantitative detection of hepatitis B virus by transcription-mediated amplification and hybridization protection assay. J Clin Microbiol 37, 310–314.
    [Google Scholar]
  15. Kao, J. H., Chen, P. J., Lai, M. Y. & Chen, D. S. ( 2000; ). Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B. Gastroenterology 118, 554–559.[CrossRef]
    [Google Scholar]
  16. Lee, C. H., Chang, S. C., Wu, C. H. & Chang, M. F. ( 2001; ). A novel chromosome region maintenance 1-independent nuclear export signal of the large form of hepatitis delta antigen that is required for the viral assembly. J Biol Chem 276, 8142–8148.[CrossRef]
    [Google Scholar]
  17. Lee, C. Z., Chen, P. J. & Chen, D. S. ( 1995; ). Large hepatitis delta antigen in packaging and replication inhibition: role of the carboxyl-terminal 19 amino acids and amino-terminal sequences. J Virol 69, 5332–5336.
    [Google Scholar]
  18. Lin, J. H., Chang, M. F., Baker, S. C., Govindarajan, S. & Lai, M. M. ( 1990; ). Characterization of hepatitis delta antigen: specific binding to hepatitis delta virus RNA. J Virol 64, 4051–4058.
    [Google Scholar]
  19. Lok, A. S., Heathcote, E. J. & Hoofnagle, J. H. ( 2001; ). Management of hepatitis B: 2000 – summary of a workshop. Gastroenterology 120, 1828–1853.[CrossRef]
    [Google Scholar]
  20. Ma, S. P., Sakugawa, H., Makino, Y., Tadano, M., Kinjo, F. & Saito, A. ( 2003; ). The complete genomic sequence of hepatitis delta virus genotype IIb prevalent in Okinawa, Japan. J Gen Virol 84, 461–464.[CrossRef]
    [Google Scholar]
  21. Makino, S., Chang, M. F., Shieh, C. K., Kamahora, T., Vannier, D. M., Govindarajan, S. & Lai, M. M. ( 1987; ). Molecular cloning and sequencing of a human hepatitis delta (δ) virus RNA. Nature 329, 343–346.[CrossRef]
    [Google Scholar]
  22. Mizokami, M., Nakano, T., Orito, E., Tanaka, Y., Sakugawa, H., Mukaide, M. & Robertson, B. H. ( 1999; ). Hepatitis B virus genotype assignment using restriction fragment length polymorphism patterns. FEBS Lett 450, 66–71.[CrossRef]
    [Google Scholar]
  23. Modahl, L. E. & Lai, M. M. ( 2000; ). Hepatitis delta virus: the molecular basis of laboratory diagnosis. Crit Rev Clin Lab Sci 37, 45–92.[CrossRef]
    [Google Scholar]
  24. Nakano, T., Shapiro, C. N., Hadler, S. C., Casey, J. L., Mizokami, M., Orito, E. & Robertson, B. H. ( 2001; ). Characterization of hepatitis D virus genotype III among Yucpa Indians in Venezuela. J Gen Virol 82, 2183–2189.
    [Google Scholar]
  25. Nakasone, H., Sakugawa, H., Shokita, H. & 8 other authors ( 1998; ). Prevalence and clinical features of hepatitis delta virus infection in the Miyako Islands, Okinawa, Japan. J Gastroenterol 33, 850–854.[CrossRef]
    [Google Scholar]
  26. Orito, E., Mizokami, M., Sakugawa, H., Michitaka, K., Ishikawa, K., Ichida, T., Okanoue, T., Yotsuyanagi, H. & Iino, S. ( 2001; ). A case–control study for clinical and molecular biological differences between hepatitis B viruses of genotypes B and C. Japan HBV Genotype Research Group. Hepatology 33, 218–223.[CrossRef]
    [Google Scholar]
  27. Rizzetto, M., Canese, M. G., Gerin, J. L., London, W. T., Sly, D. L. & Purcell, R. H. ( 1980; ). Transmission of the hepatitis B virus-associated delta antigen to chimpanzees. J Infect Dis 141, 590–602.[CrossRef]
    [Google Scholar]
  28. Saitou, N. & Nei, M. ( 1987; ). The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4, 406–425.
    [Google Scholar]
  29. Sakugawa, H., Nakasone, H., Nakayoshi, T. & 7 other authors ( 1999; ). Hepatitis delta virus genotype IIb predominates in an endemic area, Okinawa, Japan. J Med Virol 58, 366–372.[CrossRef]
    [Google Scholar]
  30. Sakugawa, H., Nakasone, H., Nakayoshi, T., Kawakami, Y., Yamashiro, T., Maeshiro, T., Kinjo, F., Saito, A. & Zukeran, H. ( 2001; ). Hepatitis B virus concentrations in serum determined by sensitive quantitative assays in patients with established chronic hepatitis delta virus infection. J Med Virol 65, 478–484.[CrossRef]
    [Google Scholar]
  31. Tamura, I., Kurimura, O., Koda, T., Ichimura, H., Katayama, S., Kurimura, T. & Inaba, Y. ( 1993; ). Risk of liver cirrhosis and hepatocellular carcinoma in subjects with hepatitis B and delta virus infection: a study from Kure, Japan. J Gastroenterol Hepatol 8, 433–436.[CrossRef]
    [Google Scholar]
  32. 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]
  33. Wang, J. G. & Lemon, S. M. ( 1993; ). Hepatitis delta virus antigen forms dimers and multimeric complexes in vivo. J Virol 67, 446–454.
    [Google Scholar]
  34. Wang, K. S., Choo, Q. L., Weiner, A. J. & 7 other authors ( 1986; ). Structure, sequence and expression of the hepatitis delta (δ) viral genome. Nature 323, 508–514.[CrossRef]
    [Google Scholar]
  35. Wu, H. N. & Lai, M. M. ( 1989; ). Reversible cleavage and ligation of hepatitis delta virus RNA. Science 243, 652–654.[CrossRef]
    [Google Scholar]
  36. Wu, J. C., Choo, K. B., Chen, C. M., Chen, T. Z., Huo, T. I. & Lee, S. D. (1995a; ). Genotyping of hepatitis D virus by restriction-fragment length polymorphism and relation to outcome of hepatitis D. Lancet 346, 939–941.[CrossRef]
    [Google Scholar]
  37. Wu, T. T., Bichko, V. V., Ryu, W. S., Lemon, S. M. & Taylor, J. M. ( 1995b; ). Hepatitis delta virus mutant: effect on RNA editing. J Virol 69, 7226–7231.
    [Google Scholar]
  38. Wu, J. C., Chiang, T. Y. & Sheen, I. J. ( 1998; ). Characterization and phylogenetic analysis of a novel hepatitis D virus strain discovered by restriction fragment length polymorphism analysis. J Gen Virol 79, 1105–1113.
    [Google Scholar]
  39. Xia, Y. P., Yeh, C. T., Ou, J. H. & Lai, M. M. ( 1992; ). Characterization of nuclear targeting signal of hepatitis delta antigen: nuclear transport as a protein complex. J Virol 66, 914–921.
    [Google Scholar]
  40. Yang, A., Papaioannou, C., Hadzyannis, S., Thomas, H. & Monjardino, J. ( 1995; ). Base changes at positions 1014 and 578 of delta virus RNA in Greek isolates maintain base pair in rod conformation with efficient RNA editing. J Med Virol 47, 113–119.[CrossRef]
    [Google Scholar]
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