Chronic hepatitis delta virus infection with genotype IIb variant is correlated with progressive liver disease

Watanabe, Hideki; Nagayama, Kazuyoshi; Enomoto, Nobuyuki; Chinzei, Ryoko; Yamashiro, Tsuyoshi; Izumi, Namiki; Yatsuhashi, Hiroshi; Nakano, Tatsunori; Robertson, Betty H.; Nakasone, Hiroki; Sakugawa, Hiroshi; Watanabe, Mamoru

doi:10.1099/vir.0.19499-0

Cited by 58 publications

(40 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%

“…In contrast, HDV isolates of genotype I have been reported in every part of the world, and the pathogenesis of genotype I infections varies from fulminant hepatitis to asymptomatic chronic liver disease (10,11,16,32,38,51,59). Phylogenetic analysis of additional HDV sequences further suggested that HDV genotype IIb (isolated from Taiwan and the Miyako Islands, Okinawa, Japan) and genotype IIb-M (isolated from the Miyako Islands) form genetic subgroups (50,60,61,65). It is worth noting that most of the above-mentioned sequences were isolated from non-African countries.…”

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confidence: 99%

“…Therefore, recent work has indicated that the various HDV genotypes fall into at least seven clades (45). Interestingly, HDV genotype I is the only genotype detected in some locations, including Europe and North America (5, 61), whereas multiple genotypes have been detected in Africa (45) and in Asian locations, including Japan, Russia, and Taiwan (16,17,33,60,61,65). Furthermore, mixed infections of genotypes I and II or II and IIb have been reported in Taiwan (66).…”

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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%

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

Wang

Chao

2005

J Virol

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“…Patients with the HDV-4 genotype frequently have mild liver disease [56]. However, a variant of the HDV-4 genotype in Japan is associated with increased progression to cirrhosis compared with that observed with the HDV-4 genotype in Taiwan [57]. …”

Section: Discussionmentioning

confidence: 99%

Characterization of the Genotypic Profile of Hepatitis Delta Virus: Isolation of HDV Genotype-1 in the Western Amazon Region of Brazil

Botelho-Souza¹,

Vieira²,

Santos³

et al. 2015

Intervirology

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The hepatitis delta virus (HDV) is a hepatotropic subvirus that is dependent on the hepatitis B virus (HBV) and supplies the viral envelope containing the surface antigen of hepatitis B. Viral genetic diversity is related to the geographical origin of the isolates, and there are at least eight genotypes that are referred to as HDV-1 through HDV-8. HDV-3 is responsible for epidemics of severe and fulminant hepatitis, which are common in northeastern South America. HDV-3 is prevalent in the Brazilian Amazon and is associated with the increased aggressiveness of HDV infections. Although isolated, the characteristics of the clinical presentation of HDV-1 in the Amazon region have not yet been clearly reported. Objective: This study aims to assess the genotypic and clinical characteristics of individuals with the HDV-1 genotype in the western Amazon region. Methods: The HDV was genotyped by nested PCR-RFLP and sequencing from serum samples of 56 patients with HBV/HDV infection. The genotypes were correlated with the clinical characteristics presented by patients with HBV/HDV infection. Results: A prevalence of 92.3% for the HDV-3 genotype (n = 48) and 7.6% (n = 4) for the HDV-1 genotype was observed. Conclusion: To date, this is the most extensive clinical study of HDV-1 genotype infections in the nonindigenous population of Western Amazonia.

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“…Genotype II and IV are seen in East Asia usually with mild disease [56]. Genotype IIB subtype from patients in Miyako Island and Okinawa have caused more severe disease than genotype IIB subtype from Taiwan [57]. HDV genotype III is seen exclusively in the Northern part of South America (Columbia, Venezuela, Peru) [3,6].…”

Section: Introductionmentioning

confidence: 99%

Delta Hepatitis

Günşar

2012

RHC

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Chronic hepatitis delta virus infection with genotype IIb variant is correlated with progressive liver disease

Cited by 58 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

Characterization of the Genotypic Profile of Hepatitis Delta Virus: Isolation of HDV Genotype-1 in the Western Amazon Region of Brazil

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