1887

Abstract

It is unclear whether the sequence populations of hepatitis C virus (HCV) quasispecies in the liver and in serum are different, as a variety of studies on this subject provide conflicting results. In the current study, the populations of HCV 5′ untranslated region (5′ UTR) sequences in paired serum and liver samples from six patients with chronic hepatitis were analysed. Liver-derived, negative-strand viral RNA was amplified with a highly strand-specific Tth-based assay, and extensive measures, including accounting for template copy number, were undertaken to lower the risk of sporadic artefactual polymorphism. Amplified sequences were compared by single-strand conformation polymorphism analysis and by direct sequencing of identified differences. In four patients, liver samples were found to contain variants within the quasispecies which were not found in serum or negative-strand viral RNA, while in the remaining two patients, low virus titre prevented a reliable quasispecies analysis. These results suggest the presence in the same individual of HCV variants differing in the 5′ UTR and possibly replicating with different kinetics.

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1999-03-01
2022-05-28
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References

  1. Agol V. I. 1991; The 5ʹ-untranslated region of picornaviral genomes. Advances in Virus Research 40:103–180
    [Google Scholar]
  2. Alter M. J., Margolis H. S., Krawczynski K., Judson F. N., Mares A., Alexander W. J., Hu P. Y., Miller J. K., Gerber M. A., Sampliner R. E., Meeks E. L., Beach M. J. 1992; The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team. New England Journal of Medicine 327:1899–1905
    [Google Scholar]
  3. Brown E. A., Zhang H., Ping L.-M., Lemon S. M. 1992; Secondary structure of the 5′ nontranslated regions of hepatitis C virus and pestivirus genomic RNAs. Nucleic Acids Research 20:5041–5045
    [Google Scholar]
  4. Cabot B., Esteban J. I., Martell M., Genesca J., Vargas V., Esteban R., Guardia J., Gomez J. 1997; Structure of replicating hepatitis C virus (HCV) quasispecies in the liver may not be reflected by analysis of circulating HCV virions. Journal of Virology 71:1732–1734
    [Google Scholar]
  5. Choo Q. L., Kuo G., Weiner A. J., Overby L. R., Bradley D. W., Houghton M. 1989; Isolation of a cDNA clone derived from a bloodborne non-A, non-B viral hepatitis genome. Science 244:359–362
    [Google Scholar]
  6. Choo Q.-L., Richman K., Han J. H., Berger K., Lee C., Dong C., Gallegos C., Coit D., Medina-Selby A., Barr P. J., Weiner A., Bradley D. W., Kuo G., Houghton M. 1991; Genetic organization and diversity of the hepatitis C virus. Proceedings of the National Academy of Sciences, USA 88:2451–2455
    [Google Scholar]
  7. Domingo E., Martinez-Salas E., Sobrino F., de la Torre J. C., Portela A., Ortin J., Lopez-Galindez C., Perez-Brena P., Villanueva N., Najera R., VandePol S., Steinhauer D., DePolo N., Holland J. 1985; The quasispecies (extremely heterogeneous) nature of viral RNA genome populations: biological relevance – a review. Gene 40:1–8
    [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. Journal of General Virology 75:1361–1369
    [Google Scholar]
  9. Hijikata M., Kato N., Ootsuyama Y., Nakagawa M., Ohkoshi S., Shimotohno K. 1991; Hypervariable regions in the putative glycoprotein of hepatitis C virus. Biochemical and Biophysical Research Communications 175:220–228
    [Google Scholar]
  10. Honda M., Kaneko S., Sakai A., Unoura M., Murakami S., Kobayashi K. 1994; Degree of diversity of hepatitis C virus quasispecies and progression of liver disease. Hepatology 20:1144–1151
    [Google Scholar]
  11. Honda M., Rijnbrand R. C. A., Amphlett A., Clarke B., Rowlands D., Lemon S. M. 1996; Structural requirements for initiation of translation by internal ribosome entry within genome-length hepatitis C virus RNA. Virology 222:31–42
    [Google Scholar]
  12. Jang S. K., Wimmer E. 1990; Cap-independent translation of encephalomyocarditis virus RNA: structural elements of the internal ribosomal entry site and involvement of a cellular 57-kD RNA–binding protein. Genes & Development 4:1560–1572
    [Google Scholar]
  13. Kiyosawa K., Sodeyama T., Tanaka E., Gibo Y., Yoshizawa K., Nakano Y., Furuta S., Akahane Y., Nishioka K., Purcell R. H., Alter H. J. 1990; Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatology 12:671–675
    [Google Scholar]
  14. Koizumi K., Enomoto E., Kurosaki M., Murakami T., Izumi N., Marumo F., Sato C. 1995; Diversity of quasispecies in various disease stages of chronic hepatitis C virus infection and its significance in interferon treatment. Hepatology 22:30–35
    [Google Scholar]
  15. Kuo G., Choo Q. L., Alter H. J., Gitnick G. L., Redeker A. G., Purcell R. H., Miyamura T., Dienstag J. L., Alter M. J., Stevens C. I., Tegtmeier G. E., Bonino F., Colombo M., Lee W. S., Kuo C., Berger K., Schuster J. R., Overby L. R., Bradley D. W., Houghton M. 1989; An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 244:362–364
    [Google Scholar]
  16. Laskus T., Wang L. F., Rakela J., Vargas H., Pinna A. D., Tsamandas A. C., Demetris A. J., Fung J. 1996; Dynamic behavior of hepatitis C virus in chronically infected patients receiving liver graft from infected donors. Virology 220:171–176
    [Google Scholar]
  17. Laskus T., Radkowski M., Wang L.-F., Cianciara J., Vargas H., Rakela J. 1997a; Hepatitis C virus negative strand RNA is not detected in peripheral blood mononuclear cells and viral sequences are identical to those in serum: a case against extrahepatic replication. Journal of General Virology 78:2747–2750
    [Google Scholar]
  18. Laskus T., Radkowski M., Wang L. F., Vargas H., Rakela J. 1997b; Lack of evidence for hepatitis G virus replication in livers of patients coinfected with hepatitis C and G viruses. Journal of Virology 71:7804–7806
    [Google Scholar]
  19. Laskus T., Radkowski M., Wang L. F., Jang S. J., Vargas H., Rakela J. 1998; Hepatitis C virus quasispecies in patients infected with HIV-1: correlation with extrahepatic viral replication. Virology 248:164–171
    [Google Scholar]
  20. Maggi F., Fornai C., Vatteroni M. L., Giorgi M., Morrica A., Pistello M., Cammarota G., Marchi S., Ciccorossi P., Bionda A., Bendinelli M. 1997; Differences in hepatitis C virus quasispecies composition between liver, peripheral blood mononuclear cells and plasma. Journal of General Virology 78:1521–1525
    [Google Scholar]
  21. Martell M., Esteban J. I., Quer J., Genesca J., Weiner A., Esteban R., Guardia J., Gomez J. 1992; Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution. Journal of Virology 66:3225–3229
    [Google Scholar]
  22. Navas S., Martin J., Quiroga J. A., Castillo I., Carreno V. 1998; Genetic diversity and tissue compartmentalization of the hepatitis C virus genome in blood mononuclear cells, liver, and serum from chronic hepatitis C patients. Journal of Virology 72:1640–1646
    [Google Scholar]
  23. Okamoto H., Sugiyama Y., Okada S., Kurai K., Akahane Y., Sugai Y., Tanaka T., Sato K., Tsuda F., Miyakawa Y., Mayumi M. 1992; Typing hepatitis C virus by polymerase chain reaction with type-specific primers: application to clinical surveys and tracing infectious sources. Journal of General Virology 73:673–679
    [Google Scholar]
  24. Pelletier J., Sonenberg N. 1988; Internal initiation of translation of eukaryotic mRNA directed by a sequence from poliovirus RNA. Nature 334:320–325
    [Google Scholar]
  25. Sakamoto N., Enomoto N., Kurosaki M., Asahina Y., Maekawa S., Koizumi K., Sakuma I., Murakami T., Marumo F., Sato C. H. 1995; Comparison of the hypervariable region of hepatitis C virus genomes in plasma and liver. Journal of Medical Virology 46:7–11
    [Google Scholar]
  26. Shimizu Y. K., Hijikata M., Iwamoto A., Alter H. J., Purcell R. H., Yoshikura H. 1994; Neutralizing antibodies against hepatitis C virus and the emergence of neutralization escape mutant viruses. Journal of Virology 68:1494–1500
    [Google Scholar]
  27. Shimizu Y. K., Igarashi H., Kanematu T., Fujiwara K., Wong D. C., Purcell R. H., Yoshikura H. 1997; Sequence analysis of the hepatitis C virus genome recovered from serum, liver, and peripheral blood mononuclear cells of infected chimpanzees. Journal of Virology 71:5769–5773
    [Google Scholar]
  28. Simmonds P., McOmish F., Yap P. L., Chan S.-W., Lin C. K., Dusheiko G., Saeed A. A., Holmes E. C. 1993; Sequence variability in the 5ʹ non-coding region of hepatitis C virus: identification of a new virus type and restrictions on sequence diversity. Journal of General Virology 74:661–668
    [Google Scholar]
  29. Simonetti R. G., Camma C., Fiorello F., Cottone M., Rapicetta M., Marino L., Fiorentino G., Craxi A., Ciccaglione A., Giuseppetti R., Stroffolini T., Pagliaro L. 1992; Hepatitis C virus infection as a risk factor for hepatocellular carcinoma in patients with cirrhosis. A case-control study. Annals of Internal Medicine 116:97–102
    [Google Scholar]
  30. Smith D. B., Mellor J., Jarvis L. M., Davidson F., Kolberg J., Urdea M., Yap P.-L., Simmonds P. The International HCV Collaborative Study Group 1995; Variation of the hepatitis C virus 5′ non-coding region: implications for secondary structure, virus detection and typing. Journal of General Virology 76:1749–1761
    [Google Scholar]
  31. Smith D. B., McAllister J., Casino C., Simmonds P. 1997; Virus ‘quasispecies’: making a mountain out of a molehill?. Journal of General Virology 78:1511–1519
    [Google Scholar]
  32. Steinhauer D. A., Holland J. J. 1987; Rapid evolution of RNA viruses. Annual Review of Microbiology 41:409–433
    [Google Scholar]
  33. Taniguchi S., Okamoto H., Sakamoto M., Kojima M., Tsuda F., Tanaka T., Munekata E., Muchmore E. E., Peterson D. A., Mishiro S. A. 1993; A structurally flexible and antigenically variable N-terminal domain of the hepatitis C virus E2/NS1 protein: implication for an escape from antibody. Virology 195:297–301
    [Google Scholar]
  34. Tsukiyama-Kohara K., Iizuka N., Kohara M., Nomoto A. 1992; Internal ribosome entry site within hepatitis C virus RNA. Journal of Virology 66:1476–1483
    [Google Scholar]
  35. Walter A. E., Turner D. H., Kim J., Lyttle M. H., Müller P., Mathews D. H., Zuker M. 1994; Coaxial stacking of helixes enhances binding of oligoribonucleotides and improves predictions of RNA folding. Proceedings of the National Academy of Sciences, USA 91:9218–9222
    [Google Scholar]
  36. Wang L.-F., Rakela J., Laskus T. 1997; Head-to-tail primer tandem repeats generated in hemi-nested PCR. Molecular & Cellular Probes 11:385–387
    [Google Scholar]
  37. Weiner A. J., Brauer M. J., Rosenblatt J., Richman K. H., Tung J., Crawford K., Bonino F., Saracco G., Choo Q. L., Houghton M., Han J. H. 1991; Variable and hypervariable domains are found in the regions of HCV corresponding to the flavivirus envelope and NS1 proteins and the pestivirus envelope glycoproteins. Virology 180:842–848
    [Google Scholar]
  38. Zeuzem S., Schmidt J. M., Lee J.-H., Ruster B., Roth W. K. 1996; Effect of interferon alpha on the dynamics of hepatitis C virus turnover in vivo. Hepatology 23:366–371
    [Google Scholar]
  39. Zuker M. 1989; On finding all suboptimal foldings of an RNA molecule. Science 244:48–52
    [Google Scholar]
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