1887

Abstract

Hepatitis B surface antigen (HBsAg) is essential for the assembly and infection of hepatitis D virus (HDV). The assembly efficiency of genotype 1 HDV is higher than that of genotype 2, whilst the P62L substitution of major HBsAg further compromises the assembly of genotype 2 and 4 HDV. This study investigated the influence of proline residues in the carboxyl end of the large hepatitis delta antigen (HDAg-L) on the assembly of HDV of different genotypes. Expression vectors containing the HDAg-L gene or full-length HDV genome of genotype 1, 2 or 4 were co-transfected with plasmids expressing HBsAg proteins that bore either proline or leucine residues at position 62. Of the eight HDV genotypes, only genotype 1 has Pro-205 in HDAg-L, whereas genotypes 2 and 4 have Arg-205. The Arg-205 to Pro-205 substitution in HDV-2 and -4 markedly increased the assembly efficiencies of HDAg-L and whole HDV genomes, even in the presence of HBsAg with Leu-62. In contrast, secretion of genotype 1 HDV or HDAg-L was reduced significantly when arginine or alanine replaced Pro-205. When HBsAg contained Pro-62, the influence of Pro-205 on assembly decreased. In conclusion, both Pro-205 of the HDAg-L and Pro-62 of the major HBsAg play critical roles in the assembly of HDV of different genotypes. The presence of Pro-205 in genotype 1 HDV may account for its higher assembly efficiencies and wider distribution.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.017541-0
2010-04-01
2019-11-17
Loading full text...

Full text loading...

/deliver/fulltext/jgv/91/4/1004.html?itemId=/content/journal/jgv/10.1099/vir.0.017541-0&mimeType=html&fmt=ahah

References

  1. 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]
  2. Castilla, A., Prieto, J. & Fausto, N. ( 1991; ). Transforming growth factors β1 and α in chronic liver disease. Effects of interferon alfa therapy. N Engl J Med 324, 933–940.[CrossRef]
    [Google Scholar]
  3. Chao, M., Hsieh, S. Y. & Taylor, J. ( 1990; ). Role of two forms of hepatitis delta virus antigen: evidence for a mechanism of self-limiting genome replication. J Virol 64, 5066–5069.
    [Google Scholar]
  4. Choi, S. H., Jeong, S. H. & Hwang, S. B. ( 2007; ). Large hepatitis delta antigen modulates transforming growth factor-β signaling cascades: implication of hepatitis delta virus-induced liver fibrosis. Gastroenterology 132, 343–357.[CrossRef]
    [Google Scholar]
  5. Chu, C. J. & Lok, A. S. ( 2002; ). Clinical significance of hepatitis B virus genotypes. Hepatology 35, 1274–1276.[CrossRef]
    [Google Scholar]
  6. Govindarajan, S., Chin, K. P., Redeker, A. G. & Peters, R. L. ( 1984; ). Fulminant B viral hepatitis: role of delta agent. Gastroenterology 86, 1417–1420.
    [Google Scholar]
  7. Govindarajan, S., De Cock, K. M. & Redeker, A. G. ( 1986; ). Natural course of delta superinfection in chronic hepatitis B virus-infected patients: histolopathologic study with multiple liver biopsies. Hepatology 6, 640–644.[CrossRef]
    [Google Scholar]
  8. Hadler, S. C., De Monzon, M., Ponzetto, A., Anzola, E., Rivero, D., Mondolfi, A., Bracho, A., Francis, D. P., Gerber, M. A. & Thung, S. ( 1984; ). Delta virus infection and severe hepatitis: an epidemic in the Yucpa Indians of Venezuela. Ann Intern Med 100, 339–344.[CrossRef]
    [Google Scholar]
  9. 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]
  10. Hwang, S. B. & Lai, M. M. C. ( 1993; ). Isoprenylation mediates direct protein–protein interactions between hepatitis large delta antigen and hepatitis B virus surface antigen. J Virol 67, 7659–7662.
    [Google Scholar]
  11. Imazeki, F., Omata, M. & Ohto, M. ( 1990; ). Heterogeneity and evolution rates of delta virus RNA sequences. J Virol 64, 5594–5599.
    [Google Scholar]
  12. Ivaniushina, V., Radjef, N., Alexeeva, M., Gault, E., Semenov, S., Salhi, M., Kiseiev, O. & Deny, P. ( 2001; ). Hepatitis delta virus genotype I and II cocirculate in an endemic area of Yakutia, Russia. J Gen Virol 82, 2709–2718.
    [Google Scholar]
  13. Jenna, S. & Sureau, C. ( 1998; ). Effect of mutations in the small envelope protein of hepatitis B virus on assembly and secretion of hepatitis delta virus. Virology 251, 176–186.[CrossRef]
    [Google Scholar]
  14. 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]
  15. Kuo, M. Y., Chao, M. & Taylor, J. ( 1989; ). Initiation of replication of the human hepatitis delta virus genome from cloned DNA: role of delta antigen. J Virol 63, 1945–1950.
    [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. Le Gal, F., Gault, E., Ripault, M. P., Serpaggi, J., Trinchet, J. C., Gordien, E. & Deny, P. ( 2006; ). Eighth major clades for hepatitis delta virus. Emerg Infect Dis 12, 1447–1450.[CrossRef]
    [Google Scholar]
  18. Miyakawa, Y. & Mizokami, M. ( 2003; ). Classifying hepatitis B virus genotypes. Intervirology 46, 329–338.[CrossRef]
    [Google Scholar]
  19. 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]
  20. Nakabayashi, H., Teketa, K., Miyano, K., Yamane, T. & Sato, J. ( 1982; ). Growth of human hepatoma cell lines with differentiated functions in chemically defined medium. Cancer Res 42, 3858–3863.
    [Google Scholar]
  21. Norder, H., Couroucé, A. M., Coursage, P., Echevarria, J. M., Lee, S. D., Mushahwar, I. K., Robertson, B. H., Locarnini, S. & Magnius, L. O. ( 2004; ). Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes. Intervirology 47, 289–309.[CrossRef]
    [Google Scholar]
  22. O'Malley, B. & Lazinski, D. W. ( 2005; ). Roles of carboxyl-terminal and farnesylated residues in the functions of the large hepatitis delta antigen. J Virol 79, 1142–1153.[CrossRef]
    [Google Scholar]
  23. Pujol, F. H. & Devesa, M. J. ( 2005; ). Genotypic variability of hepatitis viruses associated with chronic infection and the development of hepatocellular carcinoma. J Clin Gastroenterol 39, 611–618.[CrossRef]
    [Google Scholar]
  24. Rizzetto, M., Verme, G., Recchia, S., Bonino, F., Farci, P., Arico, S., Calzia, R., Picciotto, A., Colombo, M. & Popper, H. ( 1983; ). Chronic hepatitis in carriers of hepatitis B surface antigen, with intrahepatic expression of the delta antigen. An active and progressive disease unresponsive to immuno-suppressive treatment. Ann Intern Med 98, 437–441.[CrossRef]
    [Google Scholar]
  25. Sakugawa, H., Nakasone, H., Nakayoshi, T., Kawakami, Y., Miyazato, S., Kinjo, F., Saito, A., Ma, S. P., Hotta, H. & Kinoshita, M. ( 1999; ). Hepatitis delta virus genotype IIb predominates in an endemic area, Okinawa, Japan. J Med Virol 58, 366–372.[CrossRef]
    [Google Scholar]
  26. Shih, H. H., Jeng, K. S., Syu, W. J., Huang, Y. H., Su, C. W., Peng, W. L., Sheen, I. J. & Wu, J. C. ( 2008; ). Hepatitis B surface antigen levels and sequences of natural hepatitis B virus variants influence the assembly and secretion of hepatitis D virus. J Virol 82, 2250–2264.[CrossRef]
    [Google Scholar]
  27. Smedile, A., Rosina, F., Saracco, G., Chiaberge, E., Lattore, V., Fabiano, A., Brunetto, M. R., Verme, G., Rizzetto, M. & Bonino, F. ( 1991; ). Hepatitis B virus replication modulates pathogenesis of hepatitis D virus in chronic hepatitis D. Hepatology 13, 413–416.[CrossRef]
    [Google Scholar]
  28. Su, C. W., Huang, Y. H., Huo, T. I., Shih, H. H., Sheen, I. J., Chen, S. W., Lee, P. C., Lee, S. D. & Wu, J. C. ( 2006; ). Genotypes and viremia of hepatitis B and D viruses are associated with outcomes of chronic hepatitis D patients. Gastroenterology 130, 1625–1635.[CrossRef]
    [Google Scholar]
  29. Sureau, C. ( 2006; ). The role of the HBV envelope proteins in the HDV replication cycle. Curr Top Microbiol Immunol 307, 113–131.
    [Google Scholar]
  30. Taylor, J. M. ( 2003; ). Replication of human hepatitis delta virus: recent developments. Trends Microbiol 11, 185–190.[CrossRef]
    [Google Scholar]
  31. Wang, K. S., Choo, Q. L., Weiner, A. J., Ou, J. H., Najarian, R. C., Thayer, R. M., Mullenbach, G. T., Denniston, K. J., Gerin, J. L. & Houghton, M. ( 1986; ). Structure, sequence and expression of the hepatitis delta (δ) viral genome. Nature 323, 508–514.[CrossRef]
    [Google Scholar]
  32. Wu, J. C., Chen, P. J., Kuo, M. Y. P., Lee, S. D., Chen, D. S. & Ting, L. P. ( 1991; ). Production of hepatitis delta virus and suppression of helper hepatitis B virus in a human hepatoma cell line. J Virol 65, 1099–1104.
    [Google Scholar]
  33. Wu, J. C., Chen, C. L., Hou, M. C., Chen, T. Z., Lee, S. D. & Lo, K. J. ( 1994; ). Multiple viral infection as the most common cause of fulminant and subfulminant viral hepatitis in an area endemic for hepatitis B: application and limitations of the polymerase chain reaction. Hepatology 19, 836–840.[CrossRef]
    [Google Scholar]
  34. Wu, J. C., Chen, T. Z., Huang, Y. S., Yen, F. S., Ting, L. T., Sheng, W. Y., Tsay, S. H. & Lee, S. D. ( 1995a; ). Natural history of hepatitis D viral superinfection – significance of viremia detected by polymerase chain reaction. Gastroenterology 108, 796–802.[CrossRef]
    [Google Scholar]
  35. Wu, J. C., Choo, K. B., Chen, C. M., Chen, T. Z., Huo, T. I. & Lee, S. D. ( 1995b; ). Genotyping of hepatitis D virus by restriction-fragment length polymorphism and relation to outcome of hepatitis D. Lancet 346, 939–941.[CrossRef]
    [Google Scholar]
  36. 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]
  37. Yu, M. W., Yeh, S. H., Chen, P. J., Liaw, Y. F., Lin, C. L., Liu, C. J., Shih, W. L., Kao, J. H., Chen, D. S. & Chen, C. J. ( 2005; ). Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: a prospective study in men. J Natl Cancer Inst 97, 265–272.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.017541-0
Loading
/content/journal/jgv/10.1099/vir.0.017541-0
Loading

Data & Media loading...

Most Cited This Month

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