Nucleotide sequence of a cloned duck hepatitis B virus genome: comparison with woodchuck and human hepatitis B virus sequences

Mandart, Elisabeth; Kay, Alan; Galibert, Francis

doi:10.1128/jvi.49.3.782-792.1984

Cited by 283 publications

(141 citation statements)

References 35 publications

(38 reference statements)

Supporting

Mentioning

139

Contrasting

Order By: Relevance

“…The DHBV genomes used in these studies were derived from those sequenced by Mandart. 12 Sitedirected mutagenesis was used to produce a single nucleotide change, which resulted in the single amino acid change from glycine to glutamic acid at residue 133 (G133E) in the large envelope protein. 13 The coding of the DHBV polymerase open reading frame was not affected by this single nucleotide change.…”

Section: Methodsmentioning

confidence: 99%

Acute liver injury following infection with a cytopathic strain of duck hepatitis B virus

1999

View full text Add to dashboard Cite

A variant avian hepadnavirus that has been shown to destroy hepatocytes in vitro was found to be cytopathic in vivo. A single amino acid change of glycine to glutamic acid at position 133 (G133E) in the preS protein of duck hepatitis B virus (DHBV) caused an increase in the intranuclear pool of viral covalently closed circular DNA (cccDNA), resulting in a transient elevation of viral replication and eventual hepatocyte destruction. In vivo viral infection with the G133E virus was compared with infection with wild-type virus over a 72-day period. Birds were inoculated with virus at day 2 post-hatch to ensure a high percentage of infected hepatocytes and potential persistence of virus. Birds infected with the G133E virus had increased periportal cellular proliferation and numerous lysed apoptotic hepatocytes following 100% infection of hepatocytes. The liver damage within G133E virus-infected birds subsided over time, resulting in mild chronic hepatitis that was similar to that observed within wild-type virusinfected birds. The subsidence of liver damage in G133E virus-infected birds coincided with a reduction of viral cccDNA to wild-type virus levels in the liver. Our study indicates that maintenance of wild-type levels of viral cccDNA promotes persistence of virus infection by establishing a noncytopathic infection. (HEPATOLOGY 1999;29:563-571.)Hepadnaviruses cause persistent productive infections of each infected hepatocyte. During the initiation of infection, the relaxed circular DNA (rcDNA) genome in the virion is converted to covalently closed circular DNA (cccDNA) in the nucleus. Viral cccDNA is used as the template for viral RNA transcription, resulting in the production of a viral RNA molecule (pregenome) that is greater than one genome in length. The RNA pregenome is encapsidated within a viral core particle, where it is reverse-transcribed by the viralencoded DNA polymerase to produce viral minus-strand DNA. 1 Plus-strand DNA synthesis is then carried out by the same viral DNA polymerase using the viral DNA minusstrand as a template. The final DNA product contained with the capsid is a double-stranded molecule that is held in a circular conformation by a short region of base-pairing between the 5Ј end of the two strands. This form of viral DNA is referred to as relaxed circular DNA, or rcDNA. The viral capsids that contain rcDNA associate with the viral envelope proteins at the endoplasmic reticulum and are secreted as virions. Alternatively, rcDNA molecules may enter into the nucleus of the infected hepatocyte, where they are converted to additional molecules of cccDNA and cause increased levels of viral replication. The production of new viral cccDNA is regulated by the viral large envelope protein (preS) by a mechanism that has not been biochemically defined. 2 Presumably, an interaction between the preS protein and rcDNAcontaining capsids is necessary for enveloped virus formation and promotes secretion of viral rcDNA from the hepatocyte as virions. Because defects in preS that specifically inhibit ...

show abstract

Section: Methodsmentioning

confidence: 99%

Acute liver injury following infection with a cytopathic strain of duck hepatitis B virus

1999

View full text Add to dashboard Cite

show abstract

“…However, no specific integration site has been observed in human HCC suggesting that HBV may play a role in the development of neoplasia through the action of one of its gene products in trans. 3) One of the mysteries in the search for the function of the X-gene is the absence of a homologous ORF in the avian hepadnaviruses [Mandart et al, 1984;Sprengel et al, 19881, but these species may have a cellular gene performing the function served by the X-gene of the mammalian hepadnaviruses. Furthermore, the nucleotide sequence of the X ORF indicates that, like retroviral oncogenes, it has a codon usage preference favoured by eukaryotic cellular genes and not by the genes of viruses that infect these cells [Miller and Robinson, 19861.…”

Section: The Hbv Genome Encodes a Transcriptional Transactivatormentioning

confidence: 99%

Hepatitis B virus X‐gene product: A promiscuous transcriptional activator

Rossner

1992

Journal of Medical Virology

203

133

View full text Add to dashboard Cite

The disease state induced by infection with hepatitis B virus (HBV) is manifest in varying ways characterised by the extent of liver inflammation and damage and viral persistence. In a small percentage of cases, primary infection leads to fulminant hepatitis resulting in severe liver dysfunction with very high mortality. Primary infection is most often resolved by complete clearance of the virus and development of immune memory to counter reinfection, but 5‐10% of infected adults develop chronic infection characterised by the persistence of viral antigens in the serum and accompanied by varying degrees of hepatic injury. This disease state may continue after integration of HBV DNA into the hepatocyte genome from which transcription of viral antigen genes may continue in the absence of virion production. Chronically infected patients are predisposed to developing hepatocellular carcinoma (HCC) [Szmuness, 1978] with more than 100‐fold greater probability than non‐infected individuals [Beasley, et al., 1981]. Hepatitis B constitutes a major worldwide health problem with the number of chronically infected people currently estimated in excess of 250 million. HBV is the prototype member of the family of hepadnaviridae, which includes hepatitis viruses isolated from the woodchuck (WHV) [Summers et al., 1978], ground squirrel (GSHV) [Marion et al., 1980], Pekin duck (DHBV) [Mason et al., 1980], and grey heron (HHV) [Sprengel et al., 1988]. This taxonomy is derived from the relative hepatropism of virus family members, their common virion morphology, genome size, structure and organisation, and common mechanism of genome replication, which proceeds through reverse transcription of an RNA intermediate [Summers and Mason, 1982] in a manner analogous to that of retroviruses. All the viruses exhibit a strict host specificity, the human virus replicating only in man and a small number of higher apes. HBV has a partially double stranded, open‐circular genome of 3.2 kilobases (kb) which contains four open reading frames (ORFs) including the S‐gene encoding the surface antigen and the C‐gene encoding the core antigen (Fig. 1 ). A large ORF encompassing most of the viral genome encodes the viral polymerase while the fourth ORF encodes a protein of 154 amino acid residues which has been termed the X antigen (HBxAg) because the function of this product in the viral lifecycle is still under intensive investigation.

show abstract

“…Because of its small size, the HBV genome has been especially amenable to nucleotide sequence analysis. Currently, the nucleotide sequences of 11 HBV isolates (1-10) and seven isolates of HBV-related animal viruses (11)(12)(13)(14)(15)(16) have been published. In the HBV genome and in the genomes of hepadnaviruses infecting other mammals, four long open reading frames (ORFs), or regions containing codons specifying amino acids and not termination signals, have been found.…”

Section: Overlapping Gene Sequencesmentioning

confidence: 99%

Compact organization of the hepatitis B virus genome

et al. 1989

View full text Add to dashboard Cite

The genome of hepatitis B virus (HBV) is a circular DNA molecule approximately 3,200 base pairs (bp) in length. Relative to other double‐stranded DNA viruses capable of independent replication, HBV possesses the smallest genome of any virus known to infect man. Therefore, it is not surprising that HBV utilizes its genetic material economically. This is accomplished by two rare genetic arrangements: proteins are encoded from overlapping translation frames, and all regulatory signal sequences reside within protein‐encoding sequences. Thus, HBV obtains multiple use from many regions of its genome, which underscores the sophistication of this virus from an evolutionary standpoint.

show abstract

Nucleotide sequence of a cloned duck hepatitis B virus genome: comparison with woodchuck and human hepatitis B virus sequences

Cited by 283 publications

References 35 publications

Acute liver injury following infection with a cytopathic strain of duck hepatitis B virus

Acute liver injury following infection with a cytopathic strain of duck hepatitis B virus

Hepatitis B virus X‐gene product: A promiscuous transcriptional activator

Compact organization of the hepatitis B virus genome

Contact Info

Product

Resources

About