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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
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Disease relevance of Hepadnaviridae

  • State of the p53 gene in hepatocellular carcinomas of ground squirrels and woodchucks with past and ongoing infection with hepadnaviruses [1].
  • APOBEC3G (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G) is an innate intracellular antiretroviral factor that can inhibit viral retroelements such as retroviruses and hepadnaviruses [2].
  • Southern blot analysis of infected IBDE preparations using a digoxigenin-labeled positive-sense DHBV riboprobe revealed the presence of hepadnavirus covalently closed circular (CCC) DNA, minus-sense single-stranded (SS) DNA, double-stranded linear DNA, and relaxed circular DNA [3].
  • Although hepadnavirus replication occurs inside viral nucleocapsids, or cores, biochemical systems for analyzing this reaction are currently limited to unencapsidated Pols expressed in heterologous systems [4].
  • It bears homology to repetitive NLS elements previously identified near the carboxy terminus of the capsid protein of hepatitis B virus, the human prototype of the hepadnavirus family, but it maps to a more internal position [5].

High impact information on Hepadnaviridae

  • Activation of myc genes by insertion of hepadnavirus DNA now emerges as a common event in the genesis of woodchuck hepatocellular carcinoma [6].
  • Frequent activation of N-myc genes by hepadnavirus insertion in woodchuck liver tumours [6].
  • Assembly of hepadnaviruses depends on the formation of a ribonucleoprotein (RNP) complex comprising the viral polymerase polypeptide and an RNA segment, epsilon, present on pregenomic RNA [7].
  • According to the current model of hepadnavirus gene expression, the viral envelope proteins are produced from unspliced subgenomic RNAs, in contrast to the retroviral mechanism, where the subgenomic env RNA is generated by RNA splicing [8].
  • Replication initiation does not involve a nucleic acid primer; instead, the hepadnavirus P protein binds to the structured RNA encapsidation signal epsilon, from which it copies a short DNA primer that becomes covalently linked to the enzyme [9].

Chemical compound and disease context of Hepadnaviridae


Biological context of Hepadnaviridae


Anatomical context of Hepadnaviridae

  • The findings also suggest that the liver compromised by chronic hepadnavirus infection might be prone to anti-ASGPR-directed complement-mediated hepatocellular injury and that this is associated with formation of the ASGPR-anti-ASGPR immune complexes on hepatocyte surface [20].
  • The molecular characterization of Woodchuck CD28 and CTLA-4 will facilitate studies on the T-cell response to hepadnavirus in the woodchuck model [21].
  • In contrast, the amphophilic cell lineage of hepatocarcinogenesis has been observed mainly after exposure of rodents to peroxisome proliferators that are not directly DNA-reactive or to hepadnaviridae, the biochemical pattern mimicking an effect of thyroid hormone, including mitochondrial proliferation and activation of mitochondrial enzymes [22].

Gene context of Hepadnaviridae

  • Role of p50/CDC37 in hepadnavirus assembly and replication [23].
  • Recent studies on the X protein encoded by the woodchuck hepadnavirus have provided correlative evidence indicating that the interaction with DDB1 is important for establishment of infection by the virus [24].
  • APOBEC-mediated interference with hepadnavirus production [25].
  • This study indicates that antiviral cytokines, in particular IFN-gamma, may play a central role in the long-term control of occult hepadnavirus persistence in the liver [26].
  • These results suggest that p50 can function as a cellular cofactor for the hepadnavirus RT by mediating the interaction between the RT and Hsp90 [23].

Analytical, diagnostic and therapeutic context of Hepadnaviridae


  1. State of the p53 gene in hepatocellular carcinomas of ground squirrels and woodchucks with past and ongoing infection with hepadnaviruses. Rivkina, M.B., Cullen, J.M., Robinson, W.S., Marion, P.L. Cancer Res. (1994) [Pubmed]
  2. The innate antiretroviral factor APOBEC3G does not affect human LINE-1 retrotransposition in a cell culture assay. Turelli, P., Vianin, S., Trono, D. J. Biol. Chem. (2004) [Pubmed]
  3. Duck hepatitis B virus replication in primary bile duct epithelial cells. Lee, J.Y., Culvenor, J.G., Angus, P., Smallwood, R., Nicoll, A., Locarnini, S. J. Virol. (2001) [Pubmed]
  4. Generation of replication-competent hepatitis B virus nucleocapsids in insect cells. Seifer, M., Hamatake, R., Bifano, M., Standring, D.N. J. Virol. (1998) [Pubmed]
  5. Signals for bidirectional nucleocytoplasmic transport in the duck hepatitis B virus capsid protein. Mabit, H., Breiner, K.M., Knaust, A., Zachmann-Brand, B., Schaller, H. J. Virol. (2001) [Pubmed]
  6. Frequent activation of N-myc genes by hepadnavirus insertion in woodchuck liver tumours. Fourel, G., Trepo, C., Bougueleret, L., Henglein, B., Ponzetto, A., Tiollais, P., Buendia, M.A. Nature (1990) [Pubmed]
  7. Hepadnavirus assembly and reverse transcription require a multi-component chaperone complex which is incorporated into nucleocapsids. Hu, J., Toft, D.O., Seeger, C. EMBO J. (1997) [Pubmed]
  8. A splice hepadnavirus RNA that is essential for virus replication. Obert, S., Zachmann-Brand, B., Deindl, E., Tucker, W., Bartenschlager, R., Schaller, H. EMBO J. (1996) [Pubmed]
  9. Formation of a functional hepatitis B virus replication initiation complex involves a major structural alteration in the RNA template. Beck, J., Nassal, M. Mol. Cell. Biol. (1998) [Pubmed]
  10. Mutation in HBV RNA-dependent DNA polymerase confers resistance to lamivudine in vivo. Tipples, G.A., Ma, M.M., Fischer, K.P., Bain, V.G., Kneteman, N.M., Tyrrell, D.L. Hepatology (1996) [Pubmed]
  11. Adenine arabinoside monophosphate and acyclovir monophosphate coupled to lactosaminated albumin reduce woodchuck hepatitis virus viremia at doses lower than do the unconjugated drugs. Ponzetto, A., Fiume, L., Forzani, B., Song, S.Y., Busi, C., Mattioli, A., Spinelli, C., Marinelli, M., Smedile, A., Chiaberge, E. Hepatology (1991) [Pubmed]
  12. Inhibition of hepatitis B virus DNA polymerase by enantiomers of penciclovir triphosphate and metabolic basis for selective inhibition of HBV replication by penciclovir. Shaw, T., Mok, S.S., Locarnini, S.A. Hepatology (1996) [Pubmed]
  13. Inhibitory activity of dioxolane purine analogs on wild-type and lamivudine-resistant mutants of hepadnaviruses. Seignères, B., Pichoud, C., Martin, P., Furman, P., Trépo, C., Zoulim, F. Hepatology (2002) [Pubmed]
  14. In vitro model for the nuclear transport of the hepadnavirus genome. Kann, M., Bischof, A., Gerlich, W.H. J. Virol. (1997) [Pubmed]
  15. Expression of the woodchuck N-myc2 retroposon in brain and in liver tumors is driven by a cryptic N-myc promoter. Fourel, G., Transy, C., Tennant, B.C., Buendia, M.A. Mol. Cell. Biol. (1992) [Pubmed]
  16. Alpha-fetoprotein in the woodchuck model of hepadnavirus infection and disease: normal physiological patterns and responses to woodchuck hepatitis virus infection and hepatocellular carcinoma. Cote, P.J., Gerin, J.L., Tennant, B.C. Cancer Res. (1990) [Pubmed]
  17. Analysis of the earliest steps of hepadnavirus replication: genome repair after infectious entry into hepatocytes does not depend on viral polymerase activity. Köck, J., Schlicht, H.J. J. Virol. (1993) [Pubmed]
  18. Hepadnavirus P protein utilizes a tyrosine residue in the TP domain to prime reverse transcription. Weber, M., Bronsema, V., Bartos, H., Bosserhoff, A., Bartenschlager, R., Schaller, H. J. Virol. (1994) [Pubmed]
  19. Phenotypic mixing between different hepadnavirus nucleocapsid proteins reveals C protein dimerization to be cis preferential. Chang, C., Zhou, S., Ganem, D., Standring, D.N. J. Virol. (1994) [Pubmed]
  20. Modulation of the outcome and severity of hepadnaviral hepatitis in woodchucks by antibodies to hepatic asialoglycoprotein receptor. Diao, J., Slaney, D.M., Michalak, T.I. Hepatology (2003) [Pubmed]
  21. Molecular characterization of CD28 and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) of woodchuck (Marmota monax). Yang, D., Roggendorf, M., Lu, M. Tissue Antigens (2003) [Pubmed]
  22. Significance of hepatic preneoplasia for cancer chemoprevention. Bannasch, P., Nehrbass, D., Kopp-Schneider, A. IARC Sci. Publ. (2001) [Pubmed]
  23. Role of p50/CDC37 in hepadnavirus assembly and replication. Wang, X., Grammatikakis, N., Hu, J. J. Biol. Chem. (2002) [Pubmed]
  24. DDB2 induces nuclear accumulation of the hepatitis B virus X protein independently of binding to DDB1. Nag, A., Datta, A., Yoo, K., Bhattacharyya, D., Chakrabortty, A., Wang, X., Slagle, B.L., Costa, R.H., Raychaudhuri, P. J. Virol. (2001) [Pubmed]
  25. APOBEC-mediated interference with hepadnavirus production. Rösler, C., Köck, J., Kann, M., Malim, M.H., Blum, H.E., Baumert, T.F., von Weizsäcker, F. Hepatology (2005) [Pubmed]
  26. Augmented hepatic interferon gamma expression and T-cell influx characterize acute hepatitis progressing to recovery and residual lifelong virus persistence in experimental adult woodchuck hepatitis virus infection. Hodgson, P.D., Michalak, T.I. Hepatology (2001) [Pubmed]
  27. Inhibition of duck hepatitis B virus replication in vitro by 2',3'-dideoxy-3'-azidothymidine and related compounds. Suzuki, S., Lorne, D., Tyrrell, J., Saneyoshi, M. Acta Virol. (1991) [Pubmed]
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