Hepatitis delta virus cDNA sequence from an acutely HBV‐infected chimpanzee: Sequence conservation in experimental animals

Kos, Ton; Molijn, Anco; Doorn, Leen–Jan van; Belkum, Alex van; Dubbeld, Martin A.; Schellekens, Huub

doi:10.1002/jmv.1890340412

Cited by 24 publications

(10 citation statements)

References 40 publications

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“…Analysis of HDV isolates from around the world has revealed multiple phylogenetically distinct genotypes (5,16,17,33,45,60,61,65), and researchers have extensively studied the genetic heterogeneity of HDV sequences in various single-genotype infections and transfections, of both animals and cultured cells (5,12,16,26,32,36,42,55,59). Although mixed-genotype infections of HDV have been reported (66), there has been little previous work investigating the genetic diversity in mixed-genotype HDV infection.…”

Section: Resultsmentioning

confidence: 99%

RNA Recombination of Hepatitis Delta Virus in Natural Mixed-Genotype Infection and Transfected Cultured Cells

Wang

Chao

2005

J Virol

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Most RNA viruses encode their own RNA polymerases for genome replication, and increasing numbers of them appear to be capable of undergoing RNA recombination. Here, we provide the first report of intergenotypic recombination in hepatitis delta virus (HDV), the only animal RNA virus that requires host RNA polymerase(s) for viral replication. In vivo, we analyzed RNA species derived from the serum of a patient with mixed genotype I and genotype IIb HDV infection by using multiple restriction fragment length polymorphism (RFLP) assays and sequence analysis of cloned reverse transcription (RT)-PCR products. Six HDV recombinants were isolated from 101 tested clones, and HDV recombination in this patient was further confirmed by RT-PCR with genotype-specific primer pairs. Analysis of the recombination junctions suggested that the HDV genome rearrangement occurred through faithful homologous recombination. We then used an RNA cotransfection cell culture system to investigate HDV RNA recombination in vitro. We found that HDV recombinants could indeed be detected in the transfected cells; some of these possessed recombination junctions identical to those identified in vivo. Furthermore, using a PCR-independent RNase protection assay, we were able to readily identify the recombined HDV RNA species in cultured cells. Taken together, our results demonstrate that HDV RNA recombination occurs in both natural HDV infections and cultured cells, thereby presenting a novel mechanism for HDV evolution.Hepatitis delta virus (HDV) is a subviral agent of the hepatitis B virus that requires hepatitis B surface antigen for its assembly and transmission (48,49). HDV is unique among animal viruses in that it resembles some plant pathogens, such as viroids, in having a circular RNA with an unbranched rodlike structure (25, 59), and a replication strategy that utilizes host RNA polymerases (Pols) (37, 41). Upon entering a cell, genomic HDV RNA is transcribed into complementary subgenomic mRNA for the delta antigen (HDAg) (15) and multimeric antigenomic RNAs (31, 57). These then undergo selfcleavage and ligation to generate unit-length circular RNA (27,46,53,63). Similarly, the circular antigenomic RNA serves as a template for production of additional genomic RNA.In both virions and cells, the HDV RNA forms a ribonucleoprotein complex with HDAg (9, 35). There are two forms of HDAg, small and large, which play distinct biological roles. The small HDAg (195 amino acids) is required for HDV RNA replication (8,29). The large HDAg is produced through specific RNA editing by the small form of the cellular enzyme ADAR1 (20,44,62), which converts the UAG stop codon for the small HDAg into a UGG tryptophan codon (36). This process leads to translation of an additional 19 amino acids and creates the large HDAg (214 amino acids), which in turns inhibits genome replication and is required for packaging (6,8).Viral hepatitis due to HDV infection has been found worldwide, and the complete nucleotide (nt) sequences of HDV genomes have been reported from m...

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Section: Resultsmentioning

confidence: 99%

RNA Recombination of Hepatitis Delta Virus in Natural Mixed-Genotype Infection and Transfected Cultured Cells

Wang

Chao

2005

J Virol

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“…This isolate was also transmitted from chimpanzees to woodchucks and was subsequently cloned from infected woodchuck liver tissue (113). When the cloned HDV sequences were compared (108,113), the lengths were the same (1,679 bases), and also extreme sequence conservation was found (up to 98.5% homology), indicating that little change occurred as a result of serial experimental transmission. The stability of these sequences contrasts markedly with that of certain human-derived HDV sequences.…”

Section: Physicochemical Properties Of the Virionmentioning

confidence: 94%

Delta hepatitis: molecular biology and clinical and epidemiological features

et al. 1993

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Hepatitis delta virus, discovered in 1977, requires the help of hepatitis B virus to replicate in hepatocytes and is an important cause of acute, fulminant, and chronic liver disease in many regions of the world. Because of the helper function of hepatitis delta virus, infection with it occurs either as a coinfection with hepatitis B or as a superinfection of a carrier of hepatitis B surface antigen. Although the mechanisms of transmission are similar to those of hepatitis B virus, the patterns of transmission of delta virus vary widely around the world. In regions of the world in which hepatitis delta virus infection is not endemic, the disease is confined to groups at high risk of acquiring hepatitis B infection and high-risk hepatitis B carriers. Because of the propensity of this viral infection to cause fulminant as well as chronic liver disease, continued incursion of hepatitis delta virus into areas of the world where persistent hepatitis B infection is endemic will have serious implications. Prevention depends on the widespread use of hepatitis B vaccine. This review focuses on the molecular biology and the clinical and epidemiologic features of this important viral infection.

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“…The US lineages were clustered along with the strains isolated from woodchuck and chimpanzees in experimental transmission studies. These animal strains origi- nated from an Italian patient (see Kos et al 1991). The US-Z sequence isolated from a US immigrant from Romania was distantly related to the American, Italian, Middle Eastern, Asian, and Southern Pacific isolates.…”

Section: Methodsmentioning

confidence: 99%

Substitution rates in hepatitis delta virus

Krushkal

1995

J Mol Evol

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Substitution rates were estimated for the coding and noncoding regions of the hepatitis delta virus (HDV). The estimated rates of synonymous substitution in HDV were lower than the rates of substitution at non-synonymous sites and in the noncoding region. HDV has lower synonymous substitution rates than the hepatitis C virus, though both are RNA viruses. The relatively low rate of synonymous substitution in HDV may be due to a strong preference of G and C nucleotides at third codon positions. Variation in substitution rate among HDV lineages may be correlated with the clinical development of the HDV-induced hepatitis. The phylogenetic tree inferred for 24 HDV strains reveals similarities between lineages isolated from the same geographic region.

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Hepatitis delta virus cDNA sequence from an acutely HBV‐infected chimpanzee: Sequence conservation in experimental animals

Cited by 24 publications

References 40 publications

RNA Recombination of Hepatitis Delta Virus in Natural Mixed-Genotype Infection and Transfected Cultured Cells

RNA Recombination of Hepatitis Delta Virus in Natural Mixed-Genotype Infection and Transfected Cultured Cells

Delta hepatitis: molecular biology and clinical and epidemiological features

Substitution rates in hepatitis delta virus

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