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

Abstract : Frequent co-infection of hepatitis B virus genotype G with genotype A suggests it might 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 that harbors 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 encodes 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 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 genome maturity of secreted virus particles, possibly through less efficient envelopment of core particles. Co-transfection 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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Contributor : Fabien Zoulim <>
Submitted on : Friday, July 13, 2007 - 10:25:57 AM
Last modification on : Thursday, November 21, 2019 - 1:47:19 AM
Long-term archiving on: : Thursday, April 8, 2010 - 11:07:33 PM

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Ke Li, Fabien Zoulim, Christian Pichoud, Karen Kwei, Stéphanie Villet, et al.. Critical Role of the 36-nucleotide Insertion in Hepatitis B Virus Genotype G on Core Protein Expression, Genome Replication, and Virion Secretion.. Journal of Virology, American Society for Microbiology, 2007, 81 (17), pp.9202-15. ⟨10.1128/JVI.00390-07⟩. ⟨inserm-00162232⟩

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