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

• Therefore, it is possible that hepadnaviruses could develop lamivudine resistance by a similar mutation at this motif [10].
• These results indicate that the dosages of adenine arabinoside monophosphate and acyclovir monophosphate required to inhibit hepadnavirus growth can be sharply reduced by coupling the drugs to lactosaminated human serum albumin [11].
• The deoxyguanosine analog penciclovir (PCV; 9-[4-hydroxy-3-hydroxymethyl-but-1-yl]guanine), has shown potent antiviral activity against herpes viruses and hepadnaviruses [12].
• Inhibitory activity of dioxolane purine analogs on wild-type and lamivudine-resistant mutants of hepadnaviruses [13].
• In order to identify these viral proteins, we purified woodchuck hepadnavirus (WHV) core particles from infected woodchuck liver, isolated WHV DNA, and extracted the covalent complex of viral polymerase from the particles using urea [14].

Biological context of Hepadnaviridae

• The woodchuck intronless proto-oncogene N-myc2 was initially discovered as a frequent target site for hepadnavirus integration in hepatocellular carcinoma [15].
• Studies of AFP in the woodchuck model should provide opportunities to further elucidate the physiological and immunological functions of AFP and to understand virus-host cell interactions during the course of experimental hepadnavirus infection leading to HCC [16].
• Analysis of the earliest steps of hepadnavirus replication: genome repair after infectious entry into hepatocytes does not depend on viral polymerase activity [17].
• Conserved sequence motifs surrounding Tyr-96 allow the prediction of the priming tyrosine in other hepadnaviruses [18].
• Phenotypic mixing between different hepadnavirus nucleocapsid proteins reveals C protein dimerization to be cis preferential [19].

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

• In this study, we analyze the signals determining capsid compartmentalization in the duck hepatitis B virus (DHBV) animal model, as this system also allows us to study hepadnavirus infection of cultured primary hepatocytes [5].
• Antiviral agents that inhibit the reverse transcriptase activity of the hepadnavirus DNA polymerase could be potential candidates for the chemotherapy of these viruses [27].

References