Skip to content
1887

Journal of General Virology header logo Journal of General Virology

Volume 79, Issue 11

Genetic evolution of hepatitis G virus in chronically infected individual patients No Access

Abstract

Comparative sequence analysis of different isolates of hepatitis G virus (HGV) has demonstrated significant intersubject genetic heterogeneity, but few data on intrasubject genetic evolution have been reported. To further investigate the genetic diversification of the HGV genome, 36 plasma samples from eleven patients chronically infected with HGV serially obtained 2–4 years apart were analysed. We determined the viral nucleotide sequence of the 5′ non-coding (NC) and the NS3 regions by directly sequencing the RT-PCR amplified products obtained from the viral RNAs. Intrasubject sequence variation was found to be 1·3–2·4 × 10 base substitutions per genome site per year within the 5′ NC region and 1·3–9·4 × 10 base substitutions per genome site per year within the NS3 region. Depending on the genomic region analysed (i.e. 5′ NC or NS3 region), pairwise comparisons and phylogenetic reconstructions showed that intersubject genetic distances were 17·5- to 20·8-fold greater than intrasubject ones. Overall, the evolution rate of HGV in the regions analysed is not significantly different from that found in hepatitis C virus.

  • Published Online:
© Society for General Microbiology 1998
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-79-11-2623
2025-07-01
2025-07-16
Loading full text...

Full text loading...

References

  1. Alter H. J., Nakatsuji Y., Melpolder J., Wages J., Wesley R., Shih J. W., Kim J. P. 1997; The incidence of transfusion-associated hepatitis G virus infection and its relation to liver disease. New England Journal of Medicine 11:747–754
     [Google Scholar]
  2. Boom R., Sol C. J. A., Salimans M. M. M., Jansen C. L., Wertheim-Van Dillen P. M. E., Vander Nooda J. 1990; Rapid and simple methods for purification of nucleic acids. Journal of Clinical Microbiology 28:495–503
     [Google Scholar]
  3. Bukh J., Miller R. H., Purcell R. H. 1995; Genetic heterogeneity of hepatitis C virus: quasispecies and genotypes. Seminars in Liver Disease 15:41–63
     [Google Scholar]
  4. Bukh J., Kim J. F., Govindarajan S., Apgar C. L., Foung S. K. H., Wages J. Jr Yun A. J., Shapiro M., Emerson S. U., Purcell R. H. 1998; Experimental infection of chimpanzees with hepatitis G virus and genetic analysis of the virus. Journal of Infectious Diseases 177:855–862
     [Google Scholar]
  5. Domingo E., Escarmís C., Sevilla N., Moya A., Elena S. F., Quer J., Novella I. S., Holland J. J. 1996; Basic concepts in RNA virus evolution. FASEB Journal 10:859–864
     [Google Scholar]
  6. Felsenstein J. 1985; Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39:783–791
     [Google Scholar]
  7. Felsenstein J. 1988; Phylogenies from molecular sequences: inference and reliability. Annual Review of Genetics 22:521–565
     [Google Scholar]
  8. Felsenstein J. 1995; Phylogeny Inference Package (PHYLIP), version 3.57c. University of Washington, Seattle, WA, USA:
     [Google Scholar]
  9. Fukushi S., Kurihara C., Ishiyama N., Okamura H., Hoshino F. B., Oya A., Katayama K. 1996; Nucleotide sequence of the 5ʹ noncoding region of hepatitis G virus isolated from Japanese patients: comparison with reported isolates. Biochemical and Biophysical Research Communications 226:314–318
     [Google Scholar]
  10. Guilera M., Saiz J. C., López-Labrador F. X., Olmedo E., Ampurdanes S., Forns X., Bruix J., Parés A., Sánchez-Tapias J. M., JimenezdeAnta M. T., Rodés J. 1998; Hepatitis G virus infection in chronic liver disease. Gut 42:107–111
     [Google Scholar]
  11. Holland J. J. editors 1992; Genetic diversity of RNA viruses. Current Topics in Microbiology and Immunology 176:
     [Google Scholar]
  12. Ibáñez A., Gimenéz-Barcons M., Tajahuerce A., Tural C., Sirera G., Clotet B., Sánchez-Tapias J. M., Rodés J., Martínez M. A., Saiz J. C. 1998; Prevalence and genotypes of GB virus C/hepatitis G virus and hepatitis C virus (HCV) among human immunodeficiency virus (HIV) infected patients: evidence of GBV-C/HGV sexual transmission. Journal of Medical Virology 55:293–299
     [Google Scholar]
  13. Khudyakov Y. S., Cong M., Bonafonte M. T., Abdulmalek S., Nichols B. L., Lambert S., Alter M. J., Fields H. A. 1997; Sequence variation within a nonstructural region of the hepatitis G virus genome. Journal of Virology 71:6875–6880
     [Google Scholar]
  14. Kurosaki M., Enomoto N., Marumo F., Sato C. 1994; Evolution and selection of hepatitis C virus variants in patients with chronic hepatitis C. Virology 205:161–169
     [Google Scholar]
  15. Leary T. P., Muerhoff A. S., Simons J. N., Pilot-Matias T. J., Erker J. C., Chalmers M. L., Schlauder G. G., 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
     [Google Scholar]
  16. Linnen J. M., Wages J., Zhoug-Keck Z.-Y., Fry K. E., Krawczynski K., Alter H. J., Koonin E., Gallagher M., Alter M. J., Hadziyannis S., Karayannis P., Fung K., Nakatsuji Y., Shih J.W.-K., Young L., Piatak M. Jr Hoover C., Fernandez J., Chen S., Zou J.-C., Morris T., Hyams K., Ismay S., Lifson J. D., Hess G., Foung S. K. H., Thomas H., Bradley D., Margolis H., Kim J. P. 1996; Molecular cloning and association of hepatitis G virus : a transfusion-transmissible agent. Science 271:505–508
     [Google Scholar]
  17. Linnen J. M., Fung K., Fry K. E., Mizokami M., Ohba K., Wages J. M., Zhang-Keck Z. Y., Song K., Kim J. P. 1997; Sequence variation and phylogenetic analysis of the 5ʹ terminus of hepatitis G virus. Journal of Viral Hepatitis 4:293–303
     [Google Scholar]
  18. Muerhoff A. S., Simmons J. N., Leary T. P., Erker J. C., Chalmers M. L., Pilot-Matias T. J., Dawson G. J., Desai S. M., Mushahwar I. K. 1996; Sequence heterogeneity within the 5ʹ-terminal region of the hepatitis GB virus C genome and evidence for genotypes. Journal of Hepatology 25:379–384
     [Google Scholar]
  19. 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 5ʹ-untranslated and coding region sequences. Journal of Virology 71:6501–6508
     [Google Scholar]
  20. 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
     [Google Scholar]
  21. Ogata N., Alter H. J., Miller R. H., Purcell R. H. 1991; Nucleotide sequence and mutation rate of the H strain of hepatitis C virus. Proceedings of the National Academy of Sciences, USA 88:3392–3396
     [Google Scholar]
  22. 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]
  23. Page R. D. M. 1996; TREEVIEW: an application to display phylogenetic trees on personal computers. Computer Applications in the Biosciences 12:53–60
     [Google Scholar]
  24. Pessoa M. G., Terrault N. A., Detmer J., Kolberg J., Collins M., Hassoba H. M., Wright T. L. 1998; Quantitation of hepatitis G and C viruses in the liver: evidence that hepatitis G virus is not hepatotropic. Hepatology 27:877–880
     [Google Scholar]
  25. Pickering J. M., Thomas H. C., Karayiannis P. 1997; Genetic diversity between hepatitis G virus isolates : analysis of nucleotide variation in the NS-3 and putative ‘core’ peptide genes. Journal of General Virology 78:53–60
     [Google Scholar]
  26. Saiz J. C., Ampurdanés S., Olmedo E., López-Labrador F. X., Forns X., Guilera M., Tassies D., Costa J., Sánchez-Tapias J. M., Jimánez de Anta M. T., Rodás J. 1997; Hepatitis G virus infection in chronic hepatitis C : frequency, features and response to interferon. Journal of Hepatology 26:787–793
     [Google Scholar]
  27. Sakamato N., Enomoto N., Kurosaki M., Marumo F., Sato C. 1994; Sequential change of the hypervariable region of the hepatitis C virus genome in acute infection. Journal of Medical Virology 42:103–108
     [Google Scholar]
  28. Simmonds P., Smith D. B., McOmish F., Yap P. L., Kolberg J., Urdea M. S., Holmes E. C. 1994; Identification of genotypes of hepatitis C virus by sequence comparisons in the core, El and NS-5 regions. Journal of General Virology 75:1053–1061
     [Google Scholar]
  29. Simons J. N., Leary T. P., Dawson G. J., Pilot-Matias T. J., Muerhoff A. S., Schlauder G. G., Desai S. M., Mushahwar I. K. 1995; Isolation of a novel virus-like sequences associated with human hepatitis. Nature Medicine 1:564–569
     [Google Scholar]
  30. 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]
  31. Smith D. B., Cuceanu N., Davison F., Jarvis L. M., Mokili J. L., Hamid S., Ludlam C. A. 1997; Discrimination of hepatitis G virus/GBV-C geographical variants by analysis of the 5ʹ non-coding region. Journal of General Virology 78:1533–1542
     [Google Scholar]
  32. Thompson J. D., Higgins G. D., Gibson T. J. 1994; CLUSTAL W: improving the sensitivity of progressive multiple sequence alignments through sequence weighting position-specific gap penalties and weight matrix choice. Nucleic Acids Research 22:4673–4680
     [Google Scholar]
  33. Toyoda H., Fukuda Y., Koyama Y., Takamatsu J., Saito H., Hayakawa T. 1997; Effect of immunosuppression on composition of quasispecies population of hepatitis C virus in patients with chronic hepatitis C coinfected with human immunodeficiency virus. Journal of Hepatology 26:975–982
     [Google Scholar]
  34. Viazov S., Riffelmann M., Khoudyakov Y., Fields H., Varenholz C., Roggendorf M. 1997; Genetic heterogeneity of hepatitis G virus isolates from different parts of the world. Journal of General Virology 78:577–581
     [Google Scholar]
  35. Wang H. L., Hou Y. D., Jin D. Y. 1997; Identification of a single genotype of hepatitis G virus by comparison of one complete genome from a healthy carrier with eight from patients with hepatitis. Journal of General Virology 78:3247–3253
     [Google Scholar]
/content/journal/jgv/10.1099/0022-1317-79-11-2623
Loading
Genetic evolution of hepatitis G virus in chronically infected individual patients
J. Gen. Virol. 79, 2623 (2025); https://doi.org/10.1099/0022-1317-79-11-2623
/content/journal/jgv/10.1099/0022-1317-79-11-2623
/content/journal/jgv/10.1099/0022-1317-79-11-2623
Loading

Data & Media loading...

Most cited Most Cited RSS feed

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