This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tran, A Articles by Brechot, C Search for Related Content PubMed PubMed Citation Articles by Tran, A Articles by Brechot, C

 Previous Article  |  Next Article 

J Virol. 1991 July; 65(7): 3566-3574

Emergence of and takeover by hepatitis B virus (HBV) with rearrangements in the pre-S/S and pre-C/C genes during chronic HBV infection.

Institut National de la Santé et de la Recherche Médicale U.75, CHU Necker, Paris, France.

ABSTRACT

We have shown, by analyzing serial serum samples from a chronic hepatitis B virus (HBV) carrier, the emergence of HBV DNA molecules with nucleotide rearrangements in the pre-S/S and pre-C/C genes. Serum samples were obtained at four different times (1983, 1985, 1988, and 1989) from an HBsAg- and HBeAg-positive carrier with chronic hepatitis. The polymerase chain reaction was used to amplify the pre-S/S and pre-C/C genes. The amplified products were cloned, and 8 to 10 independent clones were sequenced. In 1983 and 1985 only one type of HBV DNA molecule was observed. Nucleotide divergence relative to the adw2 subtype was 4.7, 7.2, and 1.6%, for the pre-S1, pre-S2, and S regions, respectively, and 2.2 and 3.9% for the pre-C and C regions, respectively. In 1988 and 1989, HBV DNA forms with marked rearrangements of both the pre-S/S and pre-C/C regions were evidenced. In the pre-S/S region, they comprised two distinct HBV DNA molecules. The first showed nucleotide divergence of 20.4, 14.8, and 3.3% for the pre-S1, pre-S2, and S regions when compared with the adw2 sequence. In addition, nucleotide deletions in the pre-S1 region led to the appearance of a stop codon. The second was created by recombination between the original and mutated HBV DNA. In the pre-C/C region, the mutated viral DNA showed 11.7% divergence when compared with the adw2 sequence. A point mutation led to the creation of a stop codon in the pre-C region, together with an insertion of 36 nucleic acids in the core gene. Most of this DNA insertion was identical to that reported in an independent HBV isolate but showed no significant homology with known sequences. Semiquantitative estimation of the proportion of wild-type and mutated HBV DNA molecules showed a marked increase in the mutated forms during the period of follow-up. Sucrose gradient analysis indicated that the defective HBV DNA molecules were present in circulating virions. Western immunoblot analysis showed the appearance of modified translation products. Our findings thus indicate the emergence of and gradual takeover by mutated HBV DNA forms during the HBV chronic carrier state. The rearrangements we observed in the pre-S/S and pre-C/C genes might lead to changes in the immunogenicity of the viral particles and thus affect the clearance of the virus by the immune system.

This article has been cited by other articles:

• 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]  
• Li, K., Zoulim, F., Pichoud, C., Kwei, K., Villet, S., Wands, J., Li, J., Tong, S. (2007). Critical Role of the 36-Nucleotide Insertion in Hepatitis B Virus Genotype G in Core Protein Expression, Genome Replication, and Virion Secretion. J. Virol. 81: 9202-9215 [Abstract] [Full Text]  
• Simmonds, P., Midgley, S. (2005). Recombination in the Genesis and Evolution of Hepatitis B Virus Genotypes. J. Virol. 79: 15467-15476 [Abstract] [Full Text]  
• Sugauchi, F., Kumada, H., Acharya, S. A., Shrestha, S. M., Gamutan, M. T. A., Khan, M., Gish, R. G., Tanaka, Y., Kato, T., Orito, E., Ueda, R., Miyakawa, Y., Mizokami, M. (2004). Epidemiological and sequence differences between two subtypes (Ae and Aa) of hepatitis B virus genotype A. J. Gen. Virol. 85: 811-820 [Abstract] [Full Text]  
• Hou, J., Lin, Y., Waters, J., Wang, Z., Min, J., Liao, H., Jiang, J., Chen, J., Luo, K., Karayiannis, P. (2002). Detection and significance of a G1862T variant of hepatitis B virus in Chinese patients with fulminant hepatitis. J. Gen. Virol. 83: 2291-2298 [Abstract] [Full Text]  
• Kato, H., Orito, E., Gish, R. G., Sugauchi, F., Suzuki, S., Ueda, R., Miyakawa, Y., Mizokami, M. (2002). Characteristics of Hepatitis B Virus Isolates of Genotype G and Their Phylogenetic Differences from the Other Six Genotypes (A through F). J. Virol. 76: 6131-6137 [Abstract] [Full Text]  
• Kramvis, A., Weitzmann, L., Owiredu, W. K. B. A., Kew, M. C. (2002). Analysis of the complete genome of subgroup A' hepatitis B virus isolates from South Africa. J. Gen. Virol. 83: 835-839 [Abstract] [Full Text]  
• Stuyver, L., De Gendt, S., Van Geyt, C., Zoulim, F., Fried, M., Schinazi, R. F., Rossau, R. (2000). A new genotype of hepatitis B virus: complete genome and phylogenetic relatedness. J. Gen. Virol. 81: 67-74 [Abstract] [Full Text]