1887

Abstract

It is known that hepatitis D virus (HDV) requires hepatitis B virus (HBV) for supplying envelope proteins (HBsAgs) to produce mature virions, and the HDV large antigen (LDAg) is responsible for interacting with HBsAgs. However, the signal molecules involved in the cross-talk between HBsAgs and LDAg have never been reported. It has been previously demonstrated that the small form of HBsAg can facilitate the translocation of HDV large antigen green fluorescent protein (GFP) fusion protein (GFP–LD) from the nucleus to the cytoplasm. In this study, it was confirmed that the small form of HBsAg can facilitate both GFP–LD and authentic LDAg for nuclear export. It was also shown that the three forms of HBsAgs (large, middle and small) induced various rates (from 35.4 to 57.2 %) of GFP–LD nuclear export. Since HBsAgs are localized inside the endoplasmic reticulum (ER), this suggests that ER stress possibly initiates the signal for inducing LDAg translocation. This supposition is supported by results that show that around 9 % of cells appear with GFP–LD in the cytoplasm after treatment with the ER stress inducers, brefeldin A (BFA) and tunicamycin, in the absence of HBsAg. Western blot and immunofluorescence microscopy results further showed that the activation of NF-B is linked to the ER stress that induces GFP–LD translocation. Combining this with results showing that tumour necrosis factor alpha (TNF-) can also induce GFP–LD translocation, it was concluded that LDAg translocation correlates with ER stress and activation of NF-B. Nevertheless, TNF--induced GFP–LD translocation was independent of new protein synthesis, suggesting that a post-translational event occurs to GFP–LD to allow translocation.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81718-0
2006-06-01
2019-12-09
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/6/1715.html?itemId=/content/journal/jgv/10.1099/vir.0.81718-0&mimeType=html&fmt=ahah

References

  1. Bruss, V. & Ganem, D. ( 1991; ). The role of envelope proteins in hepatitis B virus assembly. Proc Natl Acad Sci U S A 88, 1059–1063.[CrossRef]
    [Google Scholar]
  2. Casey, J. L. & Gerin, J. L. ( 1995; ). Hepatitis D virus RNA editing: specific modification of adenosine in the antigenomic RNA. J Virol 69, 7593–7600.
    [Google Scholar]
  3. Chang, M.-F., Baker, S. C., Soe, L. H., Kamahora, T., Keck, J. G., Makino, S., Govindarajan, S. & Lai, M. M. C. ( 1988; ). Human hepatitis delta antigen is a nuclear phosphoprotein with RNA-binding activity. J Virol 62, 2403–2410.
    [Google Scholar]
  4. Chang, F.-L., Chen, P.-J., Tu, S.-J., Wang, C.-J. & Chen, D.-S. ( 1991; ). The large form of hepatitis delta antigen is crucial for assembly of hepatitis delta virus. Proc Natl Acad Sci U S A 88, 8490–8494.[CrossRef]
    [Google Scholar]
  5. Chang, M.-F., Chang, S. C., Chang, C.-I., Wu, K. & Kang, H.-Y. ( 1992; ). Nuclear localization signals, but not putative leucine zipper motif, are essential for nuclear transport of hepatitis delta antigen. J Virol 66, 6019–6027.
    [Google Scholar]
  6. Chao, M., Hsieh, S.-Y. & Taylor, J. ( 1990; ). Role of two forms of hepatitis delta antigen: evidence for a mechanism of self-limiting genome replication. J Virol 64, 5066–5069.
    [Google Scholar]
  7. Chau, P. K., Wang, R. Y.-L., Lin, M. H., Masuda, T., Suk, F.-M. & Shih, C. ( 2005; ). Reduced secretion of virions and hepatitis B virus (HBV) surface antigen of a naturally occurring HBV variant correlates with the accumulation of the small S envelope protein in the endoplasmic reticulum and Golgi apparatus. J Virol 79, 13483–13496.[CrossRef]
    [Google Scholar]
  8. Dimcheff, D. E., Askovic, S., Baker, A. H., Johnson-Fowler, C. & Portis, J. L. ( 2003; ). Endoplasmic reticulum stress is a determinant of retrovirus-induced spongiform neurodegeneration. J Virol 77, 12617–12629.[CrossRef]
    [Google Scholar]
  9. 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]
  10. Graham, F. L. & van der Eb, A. J. ( 1973; ). A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology 52, 456–467.[CrossRef]
    [Google Scholar]
  11. Hsieh, Y.-H., Su, I.-J., Wang, H.-C., Chang, W.-W., Lei, H.-Y., Lai, M.-D., Chang, W.-T. & Huang, W. ( 2004; ). Pre-S mutant surface antigens in chronic hepatitis B virus infection induce oxidative stress and DNA damage. Carcinogenesis 25, 2023–2032.[CrossRef]
    [Google Scholar]
  12. Hu, H.-M., Shih, K.-N. & Lo, S. J. ( 1996; ). Disulfide bond formation of the in vitro-translated large antigen of hepatitis D virus. J Virol Methods 60, 39–46.[CrossRef]
    [Google Scholar]
  13. Hung, J.-H., Su, I.-J., Lei, H.-Y. & 8 other authors ( 2004; ). Endoplasmic reticulum stress stimulates the expression of cyclooxygenase-2 through activation of NF-κB and pp38 mitogen-activated protein kinase. J Biol Chem 279, 46384–46392.[CrossRef]
    [Google Scholar]
  14. Hwang, S. B. & Lai, M. M. C. ( 1993; ). Isoprenylation mediates direct protein-protein interactions between hepatitis large delta antigen and hepatitis B surface antigen. J Virol 67, 7659–7662.
    [Google Scholar]
  15. Jayan, G. C. & Casey, J. L. ( 2002; ). Increased RNA editing and inhibition of hepatitis delta virus replication by high-level expression of ADAR1 and ADAR2. J Virol 76, 3819–3827.[CrossRef]
    [Google Scholar]
  16. Kuo, M. Y.-P., 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]
  17. Lai, M. M. C. ( 1995; ). The molecular biology of hepatitis delta virus. Annu Rev Biochem 64, 259–286.[CrossRef]
    [Google Scholar]
  18. Lai, M. M. C. ( 2005; ). RNA replication without RNA-dependent RNA polymerase: surprises from hepatitis delta virus. J Virol 79, 7951–7958.[CrossRef]
    [Google Scholar]
  19. Lee, A. S. ( 2005; ). The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods 35, 373–381.[CrossRef]
    [Google Scholar]
  20. 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 hepatitis delta antigen that is required for the viral assembly. J Biol Chem 276, 8142–8148.[CrossRef]
    [Google Scholar]
  21. Li, Y. J., Stallcup, M. R. & Lai, M. M. C. ( 2004; ). Hepatitis delta virus antigen is methylated at arginine residues, and methylation regulates subcellular localization and RNA replication. J Virol 78, 13325–13334.[CrossRef]
    [Google Scholar]
  22. Macnaughton, T. B., Shi, S. T., Modahl, L. E. & Lai, M. M. C. ( 2002; ). Rolling circle replication of hepatitis delta virus RNA is carried out by two different cellular RNA polymerases. J Virol 76, 3920–3927.[CrossRef]
    [Google Scholar]
  23. Modahl, L. E., Macnaughton, T. B., Zhu, N., Johnson, D. L. & Lai, M. M. C. ( 2000; ). RNA-dependent replication and transcription of hepatitis delta virus RNA involve distinct cellular RNA polymerase. Mol Cel Biol 20, 6030–6039.[CrossRef]
    [Google Scholar]
  24. Mu, J.-J., Wu, H.-L., Chiang, B.-L., Chang, R.-P., Chen, D.-S. & Chen, P.-J. ( 1999; ). Characterization of the phosphorylated forms and the phosphorylated residues of hepatitis delta virus delta antigens. J Virol 73, 10540–10545.
    [Google Scholar]
  25. Mu, J.-J., Chen, D.-S. & Chen, P.-J. ( 2001; ). The conserved serine 177 in the delta antigen of hepatitis delta virus is one putative phosphorylation site and is required for efficient viral RNA replication. J Virol 75, 9087–9095.[CrossRef]
    [Google Scholar]
  26. Mu, J.-J., Tsay, Y. G., Juan, L. J., Fu, T. F., Huang, W. H., Chen, D.-S. & Chen, P.-J. ( 2004; ). The small delta antigen of hepatitis delta virus is an acetylated protein and acetylation of lysine 72 may influence its cellular localization and viral RNA synthesis. Virology 319, 60–70.[CrossRef]
    [Google Scholar]
  27. 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]
  28. Reid, C. E. & Lazinski, D. W. ( 2000; ). A host-specific function is required for ligation of a wide variety of ribozyme-processed RNAs. Proc Natl Acad Sci U S A 97, 424–429.[CrossRef]
    [Google Scholar]
  29. Ryu, W. S., Bayer, M. & Taylor, J. ( 1992; ). Assembly of hepatitis delta virus particles. J Virol 66, 2310–2315.
    [Google Scholar]
  30. Ryu, W. S., Netter, H. J., Bayer, M. & Taylor, J. ( 1993; ). Ribonucleoprotein complexes of hepatitis delta virus. J Virol 67, 3281–3287.
    [Google Scholar]
  31. Sato, S., Wong, S. K. & Lazinski, D. W. ( 2001; ). Hepatitis delta virus minimal substrates competent for editing by ADAR1 and ADAR2. J Virol 75, 8547–8555.[CrossRef]
    [Google Scholar]
  32. Schröder, M. & Kaufman, R. J. ( 2005; ). ER stress and the unfolded protein response. Mutat Res 569, 29–63.[CrossRef]
    [Google Scholar]
  33. Sheu, S. Y. & Lo, S. J. ( 1992; ). Preferential ribosomal scanning is involved in the differential synthesis of the hepatitis B viral surface antigens from subgenomic transcripts. Virology 188, 353–357.[CrossRef]
    [Google Scholar]
  34. Sheu, S. Y. & Lo, S. J. ( 1994; ). Biogenesis of the hepatitis B viral middle (M) surface protein in a human hepatoma cell line: demonstration of an alternative secretion pathway. J Gen Virol 75, 3031–3039.[CrossRef]
    [Google Scholar]
  35. Sheu, S. Y., Chen, K.-L., Lee, Y.-H. W. & Lo, S. J. ( 1996; ). No intermolecular interaction between the large hepatitis delta antigens is required for the secretion with hepatitis B surface antigen: a model of empty HDV particle. Virology 218, 275–278.[CrossRef]
    [Google Scholar]
  36. Shih, K.-N. & Lo, S. J. ( 2001; ). The HDV large-delta antigen fused with GFP remains functional and provides for studying its dynamic distribution. Virology 285, 138–152.[CrossRef]
    [Google Scholar]
  37. Shih, K.-N., Chuang, Y.-T., Liu, H. & Lo, S. J. ( 2004; ). Hepatitis D virus RNA editing is inhibited by a GFP fusion protein containing a C-terminally deleted delta antigen. J Gen Virol 85, 947–957.[CrossRef]
    [Google Scholar]
  38. Su, H.-L., Liao, C.-L. & Lin, Y.-L. ( 2002; ). Japanese encephalitis virus infection initiates endoplasmic reticulum stress and an unfolded protein response. J Virol 76, 4162–4171.[CrossRef]
    [Google Scholar]
  39. Tan, K.-P., Shih, K.-N. & Lo, S. J. ( 2004; ). Ser-123 of the large antigen of hepatitis delta virus modulates its cellular localization to the nucleolus, SC-35 speckles or the cytoplasm. J Gen Virol 85, 1685–1694.[CrossRef]
    [Google Scholar]
  40. Tardif, K. D., Mori, K. & Siddiqui, A. ( 2002; ). Hepatitis C virus subgenomic replicons induce endoplasmic reticulum stress activating an intracellular signaling pathway. J Virol 76, 7453–7459.[CrossRef]
    [Google Scholar]
  41. Taylor, J. M. ( 2003; ). Replication of human hepatitis delta virus: recent developments. Trends Microbiol 11, 185–190.[CrossRef]
    [Google Scholar]
  42. Wang, H.-C., Wu, H.-C., Chen, C.-F., Fausto, N., Lei, H.-Y. & Su, I.-J. ( 2003; ). Different types of ground glass hepatocytes in chronic hepatitis B virus infection contain specific pre-S mutants that may induce endoplasmic reticulum stress. Am J Pathol 163, 2441–2449.[CrossRef]
    [Google Scholar]
  43. Wang, Y.-H., Chang, S. C., Huang, C., Li, Y.-P., Lee, C.-H. & Chang, M.-F. ( 2005; ). Novel nuclear export signal-interacting protein, NESI, critical for the assembly of hepatitis delta virus. J Virol 79, 8113–8120.[CrossRef]
    [Google Scholar]
  44. Weiner, A. J., Choo, Q.-L., Wang, K.-S., Govindarajan, S., Redeker, A. G., Gerin, J. L. & Houghton, M. ( 1988; ). A single antigenomic open reading frame of the hepatitis delta virus encodes the epitope(s) of both hepatitis delta antigen polypeptides p24 delta and p27 delta. J Virol 62, 594–599.
    [Google Scholar]
  45. Wu, C. J., Leu, C. Y., Liu, S. T., Chow, K. P., Meng, C. L. & Chang, Y. S. ( 1998; ). Transcriptional activation of NF-κB activity by Epstein–Barr virus (EBV) LMP1 as a selective therapeutic strategy for EBV-associated diseases. Gene Ther 5, 905–912.[CrossRef]
    [Google Scholar]
  46. Yeh, T.-S. & Lee, Y.-H. W. ( 1998; ). Assembly of hepatitis delta virus particles: package of multimeric hepatitis delta virus genomic RNA and the role of phosphorylation. Virology 249, 12–20.[CrossRef]
    [Google Scholar]
  47. Yeh, T.-S., Lo, S. J., Chen, P.-J. & Lee, Y.-H. W. ( 1996; ). Casein kinase II and protein kinase C modulate hepatitis delta virus RNA replication but not empty viral particle assembly. J Virol 70, 6190–6198.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81718-0
Loading
/content/journal/jgv/10.1099/vir.0.81718-0
Loading

Data & Media loading...

Supplements

vol. , part 6, pp. 1715 - 1723

Distribution pattern of GFP–LD in HuH-7 cells [PDF](25 KB)



PDF

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