Hepatitis B virus genotype G monoinfection and its transmission by blood components

Chudy, M.; Schmidt, Michael; Czudai, Volker; Scheiblauer, Heinrich; Nick, Sigrid; Mosebach, Mira; Hourfar, M. K.; Seifried, Erhard; Roth, W. Kurt; Grünelt, Elke; Nübling, C. Micha

doi:10.1002/hep.21220

Cited by 53 publications

(56 citation statements)

References 24 publications

(34 reference statements)

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“…Our experiments demonstrated that genotype G clones were replication competent whether driven by the strong actin promoter (1.1-mer genomes in pTriEx vector) or by the endogenous promoter (SphI dimers in pUC18 vector), as evidenced by RNA transcription, envelope protein expression (our unpublished observations), core protein expression and particle assembly, genome replication, and virion secretion. These findings confirm an earlier report of the replication capacity of an SpeI dimer of genotype G (25) and are fully compatible with a recent report of genotype G monoinfection in a blood donor and several transfusion recipients (12). Those authors were unable to detect genotype A sequence in blood samples by a variety of sensitive methods, thus demonstrating convincingly that genotype G can be transmitted and propagated in patients without the need for a helper virus.…”

Section: Discussionsupporting

confidence: 91%

Critical Role of the 36-Nucleotide Insertion in Hepatitis B Virus Genotype G in Core Protein Expression, Genome Replication, and Virion Secretion

Zoulim

Pichoud

et al. 2007

J Virol

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Frequent coinfection of hepatitis B virus genotype G with genotype A suggests that genotype G may require genotype A for replication or transmission. In this regard, genotype G is unique in having a 12-amino-acid extension in the core protein due to a 36-nucleotide insertion near the core gene translation initiation codon. The insertion alters base pairing in the lower stem of the pregenome encapsidation signal, which harbors the core gene initiator, and thus has the potential to affect both core protein translation and pregenomic RNA encapsidation. Genotype G is also unusual for possessing two nonsense mutations in the precore region, which together with the core gene encode a secreted nonstructural protein called hepatitis B e antigen (HBeAg). We found that genotype G clones were indeed incapable of HBeAg expression but were competent in RNA transcription, genome replication, and virion secretion. Interestingly, the 36-nucleotide insertion markedly increased the level of core protein, which was achieved at the level of protein translation but did not involve alteration in the mRNA level. Consequently, the variant core protein was readily detectable in patient blood. The 12-amino-acid insertion also enhanced the genome maturity of secreted virus particles, possibly through less efficient envelopment of core particles. Cotransfection of genotypes G and A did not lead to mutual interference of genome replication or virion secretion. Considering that HBeAg is an immunotolerogen required for the establishment of persistent infection, its lack of expression rather than a replication defect could be the primary determinant for the rare occurrence of genotype G monoinfection.

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Section: Discussionsupporting

confidence: 91%

Critical Role of the 36-Nucleotide Insertion in Hepatitis B Virus Genotype G in Core Protein Expression, Genome Replication, and Virion Secretion

Zoulim

Pichoud

et al. 2007

J Virol

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“…The presence of HBV/A significantly increases the rate of HBV/G replication in hepatocytes, although infection with HBV/G alone is possible. [46][47][48][49] Genetic rearrangements between HBV/A and HBV/G can occur during persistent coinfection. Therefore, we examined how novel Ae/G recombinants were generated and transmitted in the Japanese MSM population.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Recombinant Forms of Hepatitis B Virus Generated from Genotypes Ae and G in HIV-1-Positive Japanese Men Who Have Sex with Men

Kojima

Kawahata

Mori

et al. 2015

AIDS Research and Human Retroviruses

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The rare hepatitis B virus (HBV) genotype G (HBV/G) coinfects HIV-1-positive individuals along with HBV/A and generates recombinants. However, the circulation of HBV A/G recombinants remains poorly understood. This molecular epidemiologic study examined HBV A/G recombinants in Japanese HIV-1-positive men who have sex with men (MSM). Initially, blood specimens submitted for confirmatory tests of HIV infection in Osaka and Tokyo, Japan, from 2006 to 2013 were examined for HIV-1, and HIV-1-positive specimens were screened for HBV. Among

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“…Epidemiological and clinical data regarding this genotype are limited, likely due to the low prevalence of HBV/G throughout the world . HBV/G infection has been frequently reported to be detected along with a co-infecting functional HBV strain, such as genotype A (Kato et al, 2002a) or genotype H (Sánchez et al, 2007); however, HBV/G monoinfection has also been described (Alvarado-Esquivel et al, 2006;Chudy et al, 2006;Pas et al, 2008). Recombination between HBV/ G and the co-infecting genotype has been observed, but normally as a minority species within the HBV quasispecies population (Kato et al, 2002b).…”

mentioning

confidence: 99%

“…Clinical monoinfection with HBV/G has been suggested following LiPA analysis of an acutely infected blood donor and the corresponding platelet recipients (Chudy et al, 2006), and by LiPA analysis of Mexican (Alvarado-Esquivel et al, 2006) and European (Pas et al, 2008) chronic carriers. HBV/G has also been shown to be capable of replication in the absence of a co-infecting genotype following in vitro transfection of Huh7 cells (Li et al, 2007) or uPA/SCID mouse infection (Sugiyama et al, 2007;Tanaka et al, 2008), albeit at close to undetectable levels.…”

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confidence: 99%

Hepatitis B virus genotype G epidemiology and co-infection with genotype A in Canada

Osiowy

Gordon²,

Borlang³

et al. 2008

Journal of General Virology

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Hepatitis B virus (HBV) genotype G (HBV/G) is an unusual variant, and little is known about its epidemiology and natural history, particularly the requirement for a co-infecting HBV genotype and their relationship during infection. This study investigated the quasispecies nature of coinfecting genotypes in 39 samples collected over a 6 year period from 13 HBV/G-infected patients. HBV/G infections were found to occur predominantly in males (92 %) and were primarily associated with male homosexual sex (67 %). All patients were infected with HBV/G and HBV/A, or a recombinant HBV/A/G strain. Co-infecting genotypic prevalence was often observed to fluctuate over time, with periods of HBV/G monoinfection in some patients. The average sequence divergence among Canadian HBV/G strains was 1.57±0.62 %. Thus, all HBV/G infections in Canada occur in the context of co-infection or recombination with HBV/A, and strains display increased sequence divergence compared with all known HBV/G sequences described to date.

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Hepatitis B virus genotype G monoinfection and its transmission by blood components

Cited by 53 publications

References 24 publications

Critical Role of the 36-Nucleotide Insertion in Hepatitis B Virus Genotype G in Core Protein Expression, Genome Replication, and Virion Secretion

Critical Role of the 36-Nucleotide Insertion in Hepatitis B Virus Genotype G in Core Protein Expression, Genome Replication, and Virion Secretion

Identification of Novel Recombinant Forms of Hepatitis B Virus Generated from Genotypes Ae and G in HIV-1-Positive Japanese Men Who Have Sex with Men

Hepatitis B virus genotype G epidemiology and co-infection with genotype A in Canada

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