STRUCTURE AND REPLICATION OF HEPATITIS DELTA VIRUS

Summary

Principal Investigator: John Taylor
Affiliation: Fox Chase Cancer Center
Country: USA
Abstract: The goal of this proposal is to contribute to the eventual understanding of how reverse transcriptase participates in the generation, in germ line cells, of Alu-like elements and processed genes. One group of aims is to pursue the observation that in the endogenous RNA-directd DNA snythesis of melittin-disrupted quail-grown retrovirus, the cellular 7S-L RNA is reverse transcribed using a tRNA-sized primer to generate a major discrete 130b species of DNA. This observation is doubly tantalizing. Firstly, it suggests an analogy to the early events in the reverse transcription of the avian retroviral genome in whch tRNA.trp is used as primer for the transcription of a specific 101b species from the 5'-end of the RNA genome. Secondly, it suggests that the observed reverse transcription of 7S-L RNA may be a step in the process by which the DNA of eucaryotic cells has accumulated multiple copies of what are referred to as Alu-like elements. This suggestion is made because such elements are fequently about 130b long and show significant sequence-relatedness to the 5'-terminus of the 7S-L RNA. The studies proposed will therefore test for 7S-L RNA the hypothesis of others that reverse transcription of cellular RNA's may be involved not only in the generation and transmission of Alu-like elements but also of certain pseudogenes, processed genes and gene conversion events. Such phenomena are all analogous to the formation of endogenous retrovirus-like DNA elements in that they could require, albeit rarely, reverse transcription events to take place in germ line cells. For this reason the second group of aims are directed at potential sources of reverse transcriptase in the quail. By high stringency hybridization the quail is free of DNA related to the reverse transcriptase of avian leukosis virus. However, with lowered stringency it has been possible to detect and clone in a lambda vector sequences that are related to the retroviral polymerase gene. The structure of these sequences will be determined and their expression as RNA assayed in quail embryonic tissues. The sequences will also be tested for relationship to those of the retrovirus-like particles, reportedly released from embryonic quail tissues, in the studies of Hofschneider and coworkers.
Funding Period: 1978-09-30 - 1994-03-31
more information: NIH RePORT

Top Publications

  1. ncbi Reconstitution in cultured cells of replicating HDV RNA from pairs of less than full-length RNAs
    Severin O Gudima
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA
    RNA 11:90-8. 2005
  2. ncbi Intracellular localization of hepatitis delta virus proteins in the presence and absence of viral RNA accumulation
    Ziying Han
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111 2497, USA
    J Virol 83:6457-63. 2009
  3. ncbi Liver-specific microRNA miR-122 enhances the replication of hepatitis C virus in nonhepatic cells
    Jinhong Chang
    Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, 3805 Old Easton Road, Doylestown, PA 18902, USA
    J Virol 82:8215-23. 2008
  4. ncbi Properties of subviral particles of hepatitis B virus
    Ning Chai
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111 2497, USA
    J Virol 82:7812-7. 2008
  5. ncbi Transcription of hepatitis delta virus RNA by RNA polymerase II
    Jinhong Chang
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111 2497, USA
    J Virol 82:1118-27. 2008
  6. ncbi Structure and replication of hepatitis delta virus RNA
    J M Taylor
    Fox Chase Cancer Center, Philadelphia, PA 19111 2497, USA
    Curr Top Microbiol Immunol 307:1-23. 2006
  7. ncbi Restoration in vivo of defective hepatitis delta virus RNA genomes
    Severin O Gudima
    Fox Chase Cancer Center, Philadephia, Pennsylvania 19111, USA
    RNA 12:1061-73. 2006
  8. ncbi Action of inhibitors on accumulation of processed hepatitis delta virus RNAs
    Jinhong Chang
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA
    J Virol 80:3205-14. 2006
  9. ncbi Hepatitis delta virus
    John M Taylor
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111 2497, USA
    Virology 344:71-6. 2006
  10. ncbi Evolution of hepatitis delta virus RNA genome following long-term replication in cell culture
    Jinhong Chang
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111 2497
    J Virol 79:13310-6. 2005

Scientific Experts

  • John Taylor
  • Jinhong Chang
  • Severin O Gudima
  • Ziying Han
  • Ning Chai
  • Carolina Alves
  • Severin Gudima
  • Michal Jarnik
  • Ho Eun Chang
  • Emmanuelle Nicolas

Detail Information

Publications12

  1. ncbi Reconstitution in cultured cells of replicating HDV RNA from pairs of less than full-length RNAs
    Severin O Gudima
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA
    RNA 11:90-8. 2005
    ....
  2. ncbi Intracellular localization of hepatitis delta virus proteins in the presence and absence of viral RNA accumulation
    Ziying Han
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111 2497, USA
    J Virol 83:6457-63. 2009
    ..These studies provide evidence that deltaAg does not interact directly with either Pol II or nucleolin and that forms of deltaAg which support replication are also capable of prior nucleolar transit...
  3. ncbi Liver-specific microRNA miR-122 enhances the replication of hepatitis C virus in nonhepatic cells
    Jinhong Chang
    Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, 3805 Old Easton Road, Doylestown, PA 18902, USA
    J Virol 82:8215-23. 2008
    ..Therefore, we conclude that although miR-122 is not absolutely required, it greatly enhances HCV replication in nonhepatic cells...
  4. ncbi Properties of subviral particles of hepatitis B virus
    Ning Chai
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111 2497, USA
    J Virol 82:7812-7. 2008
    ..However, unlike soluble forms of HBV envelope protein that were potent inhibitors, the SVP did not inhibit the ability of HBV and HDV to infect primary human hepatocytes...
  5. ncbi Transcription of hepatitis delta virus RNA by RNA polymerase II
    Jinhong Chang
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111 2497, USA
    J Virol 82:1118-27. 2008
    ..Findings include evidence that HDV replication is somehow able to direct the available delta antigen to sites in the nucleoplasm, almost exclusively colocalized with Pol II in what others have described as transcription factories...
  6. ncbi Structure and replication of hepatitis delta virus RNA
    J M Taylor
    Fox Chase Cancer Center, Philadelphia, PA 19111 2497, USA
    Curr Top Microbiol Immunol 307:1-23. 2006
    ..One theme of this review is that such models, even after some revision, deceptively simplify the complexity of HDV replication and can fail to make clear major questions yet to be solved...
  7. ncbi Restoration in vivo of defective hepatitis delta virus RNA genomes
    Severin O Gudima
    Fox Chase Cancer Center, Philadephia, Pennsylvania 19111, USA
    RNA 12:1061-73. 2006
    ....
  8. ncbi Action of inhibitors on accumulation of processed hepatitis delta virus RNAs
    Jinhong Chang
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA
    J Virol 80:3205-14. 2006
    ....
  9. ncbi Hepatitis delta virus
    John M Taylor
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111 2497, USA
    Virology 344:71-6. 2006
    ..It starts with a brief overview of HDV and its replication, notes some of the major unresolved questions, and directs the interested reader to more detailed reviews...
  10. ncbi Evolution of hepatitis delta virus RNA genome following long-term replication in cell culture
    Jinhong Chang
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111 2497
    J Virol 79:13310-6. 2005
    ..A model is provided to explain how, in this experimental system, the observed single-nucleotide changes were essentially neutral in terms of their effect on the ability of the HDV genome to carry out continued rounds of replication...
  11. ncbi Development of a novel system to study hepatitis delta virus genome replication
    Jinhong Chang
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111-2497, USA
    J Virol 79:8182-8. 2005
    ..These findings and those of other studies that are under way demonstrate the potential applications of this experimental system...
  12. ncbi Chapter 3. Replication of the hepatitis delta virus RNA genome
    John M Taylor
    Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
    Adv Virus Res 74:103-21. 2009
    ..This chapter is concerned with recent developments in our understanding of the genome replication process...