Complete Genomes, Phylogenetic Relatedness, and Structural Proteins of Six Strains of the Hepatitis B Virus, Four of Which Represent Two New Genotypes

Nordér, Helené; Couroucé, Anne‐Marie; Magnius, Lars O.

doi:10.1006/viro.1994.1060

Cited by 723 publications

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“…HBV has approximately 3,200 bases that can be divided into several genotypes by sequence divergence, with 8 genotypes (A-H) reported [Okamoto et al, 1988;Norder et al, 1994;Stuyver et al, 2000;Arauz-Ruiz et al, 2002]. These genotypes have a distinct geographical distribution, with genotypes A (HBV/A) and HBV/ D predominant in Europe, Middle East, Central Asia, Siberia, and America, HBV/B and HBV/C in East Asia, and HBV/E in Africa.…”

Section: Introductionmentioning

confidence: 99%

Tracing the history of hepatitis B virus genotype D in western Japan

Michitaka

Tanaka

Horiike

et al. 2005

Journal of Medical Virology

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The major hepatitis B virus (HBV) genotypes in Japan are B and C. HBV genotype D (HBV/D), however, is widespread in a small area of Western Japan, where the Gianotti-Crosti syndrome caused by HBV subtype ayw, which is suspected to be HBV/D, was endemic in the 1970s. The aim of the study was to elucidate its origin, time of transmission, and spread in this area. Genotyping of HBV-DNA was done in 363 patients with HBV infection. The year of birth was checked in patients with HBV/D. The full genome sequences of 20 HBV/D strains, 2 of which were obtained from a single carrier with a 19-yearinterval, were analyzed. An evolutionary rate, the date of the most recent common ancestor, and the effective number of HBV/D infections were calculated. Fifty-two of 363 patients were infected with HBV/D, and 39 were born in 1970s. In a phylogenetic tree, the 20 HBV/D strains produced a definite cluster, and the evolutionary rate was calculated to be 5.4 Â 10 À5 nucleotide substitutions/site/year. The root of the tree was estimated to be in approximately 1,900 and began to spread from the 1940s, leading to a rapid increase of infected patients in the 1970s. From these results, it is suspected that HBV/D was likely transmitted to the area investigated approximately 100 years ago and then spread widely in the 1970s. From the history of the area and the genetic analysis, HBV/ D in this area was speculated to be of Russian origin.

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Section: Introductionmentioning

confidence: 99%

Tracing the history of hepatitis B virus genotype D in western Japan

Michitaka

Tanaka

Horiike

et al. 2005

Journal of Medical Virology

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“…These amino acid changes were already observed before therapy and remained stable at the end of the 16 weeks therapy, suggesting that these variations were linked to the spontaneous heterogeneity of the viral genome. 33 All three patients had a partial response to famciclovir therapy with a decrease of viral DNA titers greater than 50%. These findings indicate that the absence of viral DNA clearance from serum in these patients was not associated with a particular viral genotype nor with the selection of polymerase gene mutants.…”

Section: Comparison With Patients Treated With Famciclovir For 16 Weementioning

confidence: 99%

Transient Selection of A Hepatitis B Virus Polymerase Gene Mutant Associated With A Decreased Replication Capacity and Famciclovir Resistance

et al. 1999

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Prolonged therapy for chronic hepatitis B (HBV) with nucleoside analogs may result in the emergence of HBV mutants resistant to antivirals. Here, we describe the transient selection of an HBV polymerase gene mutant that was associated with viral persistence in an immune competent patient treated with famciclovir. Viral polymerase gene sequence was analyzed directly on polymerase chain reaction (PCR) products and also after cloning. The results showed the transient selection of a V542I mutant in the C domain of the viral polymerase. This mutation was associated with a stop codon at amino acid position 199 in the overlapping S gene. The mutated sequence was subcloned in a vector expressing the entire HBV pregenome to study its replication capacity after transient transfection in cultured hepatoma cells. The results showed that the V542I mutant has a decreased replication capacity compared with wild type virus and does not produce HBsAg. The sensitivity of the V542I mutant to penciclovir, the active metabolite of famciclovir, was further studied in tissue culture. This mutant was shown to be resistant to penciclovir, but remained sensitive to lamivudine, as was subsequently observed in vivo. Recently, the antiviral efficacy of new nucleoside analogs, famciclovir and lamivudine, has been assessed in chronically hepatitis B virus (HBV)-infected patients. 1,2 Famciclovir is the oral prodrug of penciclovir (9-[4-hydroxy-3 hydroxymethylbut-1-yl] guanine; BRL 39123)-triphosphate, which was shown to inhibit hepadnavirus replication in vitro in tissue culture and in vivo in animal models of HBV infection. 3,4 It was further shown that penciclovir triphosphate not only inhibits the DNA dependent DNA polymerase activity of the HBV polymerase, 5 but also the RNA-dependent activity of this enzyme, i.e., reverse transcription, by inhibiting the synthesis of the short DNA primer for reverse transcription. 6 Preliminary evidence suggested that famciclovir may have clinical utility in the treatment of chronic hepatitis B patients 7 and in orthotopic liver transplant patients. 8 A first placebocontrolled pilot study showed a fall of HBV DNA levels by more than 90% in 6 out of 11 evaluable patients. 7 Kruger et al. have reported, in 11 patients with HBV recurrence after orthotopic liver transplantation, that famciclovir treatment could induce a significant decrease of serum viral DNA levels in 90% of the patients and a clearance of HBV DNA detected by PCR in 36%, without significant side effect. 8 A large multicenter placebo controlled trial including 333 patients showed the clinical efficacy of a 16-week course of famciclovir with a dose-dependent antiviral effect accompanied by a decrease of serum ALT levels and a significant increase of anti-HBe antibody seroconversion compared with the placebo group. 9 By using the results of clinical trials for the evaluation of another promising nucleoside analog, lamivudine (3TC or [(Ϫ)-␤-L-2Ј, 3Ј-Dideoxy-3Јthiacytidine]), Nowak et al. have determined the kinetics of viral clearance during an...

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“…High genetic variability is another feature typical of HBV, related to the absence of proofreading activity of the viral polymerase during the reverse transcription step of genome replication. To date, eight genotypes (A-H) have been established based on intergroup divergence of .7.5 % in the complete nucleotide sequence (Arauz-Ruiz et al, 2002;Kramvis et al, 2008;Norder et al, 1994;Okamoto et al, 1988;Stuyver et al, 2000). Recently, a ninth genotype isolated in Laos (Olinger et al, 2008a) and Vietnam (Hannoun et al, 2000;Olinger et al, 2008b;Tran et al, 2008) and tentatively termed 'I' was proposed, although it is still subject to debate (Kurbanov, 2008).…”

Section: Introductionmentioning

confidence: 99%

A novel hepatitis B virus (HBV) subgenotype D (D8) strain, resulting from recombination between genotypes D and E, is circulating in Niger along with HBV/E strains

Chekaraou

Brichler

Mansour

et al. 2010

Journal of General Virology

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Niger is a west African country that is highly endemic for hepatitis B virus (HBV) infection. The seroprevalence for HBV surface antigen (HBsAg) is about 20 %; however, there are no reports on the molecular epidemiology of HBV strains spreading in Niger. In the present study, HBV isolates from the sera of 58 consecutive, asymptomatic, HBsAg-positive blood donors were characterized. Genotype affiliation was determined by amplification, sequencing and phylogenetic analysis of the preS1, polymerase/reverse transcriptase (RT/Pol) and precore (preC)/C regions. The first series of results revealed that different genomic fragments clustered with different genotypes on phylogenetic trees, suggesting recombination events. Twenty-four complete genomic sequences were obtained by amplification and sequencing of seven overlapping regions covering the whole genome, and were studied by extensive phylogenetic analysis. Among them, 20 (83.3 %) were classified unequivocally as genotype E (HBV/E). The remaining four (16.7%) clustered on a distinct branch within HBV/D with strong bootstrap and posterior probability values. Complete molecular characterization of these four strains was achieved by the Simplot program, bootscanning analysis and cloning experiments, and enabled us to identify an HBV/D-E recombinant that formed a new HBV/D subgenotype spreading in Niger, tentatively named D8. Moreover, 20 new complete HBV/E nucleotide sequences were determined that exhibited higher genetic variability than is generally described in Africa. One was found to be a recombinant containing HBV/D sequences in the preS2 and RT/Pol regions. Taken together, these data suggest that, in Niger, genetic variability of HBV strains is still evolving, probably reflecting ancient endemic HBV infection. INTRODUCTIONHepatitis B virus (HBV) infection remains a major public health problem, particularly in Africa, although data for precisely estimating the burden of HBV infection are lacking. It is estimated that 2 billion people worldwide are or have been infected with HBV (WHO: http://www.who. int/csr/disease/hepatitis/HepatitisB_whocdscsrlyo2002_2.pdf), among whom over 360 million are in a chronic carrier state with a high risk of developing cirrhosis and hepatocellular carcinoma (Ganem & Prince, 2004;Lee et al., 1997;Lok, 2004). About 70-140 million of these carriers live in Africa, and about 250 000 of the 1.3 million HBV-related deaths recorded each year throughout the world occur in Africa (Andernach et al., 2009;Hubschen et al., 2008;Kramvis & Kew, 2007;Kramvis et al., 2002;Mulders et al., 2004). HBV belongs to the family Hepadnaviridae and is characterized by a partially double-stranded circular DNA genome of 3These authors contributed equally to this work.The GenBank/EMBL/DDBJ accession numbers for the sequences determined in this study are FN594748-FN594771.A supplementary list of additional GenBank sequences used in this study is available with the online version of this paper. RESULTS Nucleotide sequences and phylogenetic analysesSeveral nucleot...

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Complete Genomes, Phylogenetic Relatedness, and Structural Proteins of Six Strains of the Hepatitis B Virus, Four of Which Represent Two New Genotypes

Cited by 723 publications

References 0 publications

Tracing the history of hepatitis B virus genotype D in western Japan

Tracing the history of hepatitis B virus genotype D in western Japan

Transient Selection of A Hepatitis B Virus Polymerase Gene Mutant Associated With A Decreased Replication Capacity and Famciclovir Resistance

A novel hepatitis B virus (HBV) subgenotype D (D8) strain, resulting from recombination between genotypes D and E, is circulating in Niger along with HBV/E strains

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