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Journal of Virology, September 2007, p. 9202-9215, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00390-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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

Ke Li,1 Fabien Zoulim,2,3* Christian Pichoud,2 Karen Kwei,1 Stéphanie Villet,2,3 Jack Wands,1 Jisu Li,1 and Shuping Tong1*

Liver Research Center, Rhode Island Hospital, Brown University, Providence, Rhode Island,1 INSERM, U871, 69003 Lyon, France,2 Université Lyon 1, IFR62 Lyon-Est, 69008 Lyon, France3

Received 23 February 2007/ Accepted 31 May 2007

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.

* Corresponding author. Mailing address for Fabien Zoulim: INSERM Unit 871, 151 Cours Albert Thomas, 69003 Lyon, France. Phone: 33472681970. Fax: 33472681971. E-mail: zoulim{at}lyon.inserm.fr. Mailing address for Shuping Tong: Liver Research Center, Rhode Island Hospital, Brown University, 55 Claverick St., 4th Floor, Providence, RI 02903. Phone: (401) 444-7365. Fax: (401) 444-2939. E-mail: Shuping_Tong_MD{at}Brown.edu

{triangledown} Published ahead of print on 13 June 2007.

Journal of Virology, September 2007, p. 9202-9215, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00390-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • Osiowy, C., Gordon, D., Borlang, J., Giles, E., Villeneuve, J.-P. (2008). Hepatitis B virus genotype G epidemiology and co-infection with genotype A in Canada. J. Gen. Virol. 89: 3009-3015 [Abstract] [Full Text]  


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