1887

Abstract

The function of the X protein (pX) in the replication cycle of mammalian hepadnaviruses is enigmatic. Using tissue culture experiments it has been shown that the X gene product is not central to hepatitis B virus (HBV) replication and virion export. However, at present it is still unclear whether this also applies to the situation. Using a terminally redundant X-deficient HBV DNA construct, transgenic mice were established that exhibited high-level expression of the viral core protein in liver and kidneys. Importantly, replicative DNA intermediates and mature viral genomes could be detected in the liver and serum of these mice, respectively. These findings indicate that, in the model of transgenic mice, the HBV X (HBx) gene product is not required for HBV replication and virion secretion.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-83-5-991
2002-05-01
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/83/5/0830991a.html?itemId=/content/journal/jgv/10.1099/0022-1317-83-5-991&mimeType=html&fmt=ahah

References

  1. Blum H. E., Zhang Z. S., Galun E., von-Weizsacker F., Garner B., Liang T. J., Wands J. R. 1992; Hepatitis B virus X protein is not central to the viral life cycle in vitro. Journal of Virology 66:1223–1227
    [Google Scholar]
  2. Chen H., Kaneko S., Girones R., Anderson R., Hornbuckle W., Tennant B., Cote P., Gerin J., Purcell R., Miller R. 1993; The woodchuck hepatitis virus X gene is important for establishment of virus infection in woodchucks. Journal of Virology 67:1218–1226
    [Google Scholar]
  3. Colgrove R., Simon G., Ganem D. 1989; Transcriptional activation of homologous and heterologous genes by the hepatitis B virus X gene product in cells permissive for viral replication. Journal of Virology 63:4019–4026
    [Google Scholar]
  4. Dandri M., Schirmacher P., Rogler C. E. 1996; Woodchuck hepatitis virus X protein is present in chronically infected woodchuck liver and woodchuck hepatocellular carcinomas which are permissive for viral replication. Journal of Virology 70:5246–5254
    [Google Scholar]
  5. Guidotti L. G., Matzke B., Schaller H., Chisari F. V. 1995; High-level hepatitis B virus replication in transgenic mice. Journal of Virology 69:6158–6169
    [Google Scholar]
  6. Guidotti L. G., Matzke B., Pasquinelli C., Shoenberger J. M., Rogler C. E., Chisari F. V. 1996; The hepatitis B virus precore protein inhibits HBV replication in transgenic mice. Journal of Virology 70:7056–7061
    [Google Scholar]
  7. Guo W., Chen M., Yen T. S., Ou J. H. 1993; Hepatocyte-specific expression of the hepatitis B virus core promoter depends on both positive and negative regulation. Molecular and Cellular Biology 13:443–448
    [Google Scholar]
  8. Hogan B., Beddington R., Costantini F., Lacy E. 1994 Manipulating the Mouse Embryo: a Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  9. Hsu S., Raine L., Fanger H. 1981; Use of avidin–biotin–peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabelled antibody (PAP) procedures. Journal of Histochemistry and Cytochemistry 29:577–580
    [Google Scholar]
  10. Kim C. M., Koike K., Saito I., Miyamura T., Jay G. 1991; HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature 351:317–320
    [Google Scholar]
  11. Koike K., Shirakata Y., Yaginuma K., Arii M., Takada S., Nakamura I., Hayashi Y., Kawada M., Kobayashi M. 1989; Oncogenic potential of hepatitis B virus. Molecular Biology and Medicine 6:151–160
    [Google Scholar]
  12. Lee T. H., Finegold M. J., Shen R. F., DeMayo J. L., Woo S. L., Butel J. S. 1990; Hepatitis B virus transactivator X protein is not tumorigenic in transgenic mice. Journal of Virology 64:5939–5947
    [Google Scholar]
  13. Levrero M., Stemler M., Pasquinelli C., Alberti A., Jean-Jean O., Franco A., Balsano C., Diop D., Brechot C., Melegari M. and others 1991; Significance of anti-HBx antibodies in hepatitis B virus infection. Hepatology 13:143–149
    [Google Scholar]
  14. Madden C. R., Finegold M. J., Slagle B. L. 2001; Hepatitis B virus X protein acts as a tumor promoter in development of diethylnitrosamine-induced preneoplastic lesions. Journal of Virology 75:3851–3858
    [Google Scholar]
  15. Murakami S. 1999; Hepatitis B virus X protein: structure, function and biology. Intervirology 42:81–99
    [Google Scholar]
  16. Nassal M. 1992; The arginine-rich domain of the hepatitis B virus core protein is required for pregenome encapsidation and productive viral positive-strand DNA synthesis but not for virus assembly. Journal of Virology 66:4107–4116
    [Google Scholar]
  17. Pfaff E., Salfeld J., Gmelin K., Schaller H., Theilmann L. 1987; Synthesis of the X-protein of hepatitis B virus in vitro and detection of anti-X antibodies in human sera. Virology 158:456–460
    [Google Scholar]
  18. Reifenberg K., Löhler J., Pudollek H. P., Schmitteckert E., Spindler G., Köck J., Schlicht H. J. 1997; Long term expression of the hepatitis B virus core- e- and X-proteins does not cause organ pathology in transgenic mice. Journal of Hepatology 26:119–130
    [Google Scholar]
  19. Reifenberg K., Wilts H., Löhler J., Nusser P., Hanano R., Guidotti L. G., Chisari F. V., Schlicht H. J. 1999; The hepatitis B virus X-protein transactivates viral core gene expression in vivo. Journal of Virology 73:10399–10405
    [Google Scholar]
  20. Rossner M. 1992; The hepatitis B virus x-gene product: a promiscuous transcriptional activator. Journal of Medical Virology 36:101–117
    [Google Scholar]
  21. Schlicht H. J., Schaller H. 1989; The secretory core protein of human hepatitis B virus is expressed on the cell surface. Journal of Virology 63:5399–5404
    [Google Scholar]
  22. Spandau D. F., Lee C. H. 1988; Trans-activation of viral enhancers by the hepatitis B virus X protein. Journal of Virology 62:427–434
    [Google Scholar]
  23. Su Q., Schroder C. H., Hofmann W. J., Otto G., Pichlmayr R., Bannasch P. 1998; Expression of hepatitis B virus X protein in HBV-infected human livers and hepatocellular carcinomas. Hepatology 27:1109–1120
    [Google Scholar]
  24. Yaginuma K., Shirakata Y., Kobayashi M., Koike K. 1987; Hepatitis B virus (HBV) particles are produced in a cell culture system by transient expression of transfected HBV DNA. Proceedings of the National Academy of Sciences, USA 84:2678–2682
    [Google Scholar]
  25. Zahm P., Hofschneider P. H., Koshy R. 1988; The HBV X-ORF encodes a transactivator: a potential factor in viral hepatocarcinogenesis. Oncogene 3:169–177
    [Google Scholar]
  26. Zoulim F., Saputelli J., Seeger C. 1994; Woodchuck hepatitis virus X protein is required for viral infection in vivo. Journal of Virology 68:2026–2030
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-83-5-991
Loading
/content/journal/jgv/10.1099/0022-1317-83-5-991
Loading

Data & Media loading...

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