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

 Previous Article  |  Next Article 

Journal of Virology, November 2006, p. 10307-10314, Vol. 80, No. 21
0022-538X/06/$08.00+0     doi:10.1128/JVI.00996-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Molecular Evolution of Hepatitis B Virus over 25 Years

Carla Osiowy,1* Elizabeth Giles,1 Yasuhito Tanaka,2 Masashi Mizokami,2 and Gerald Y. Minuk3

National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada,1 Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho, Nagoya, Japan,2 Section of Hepatology, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada3

Received 15 May 2006/ Accepted 3 August 2006

Determining the longitudinal molecular evolution of hepatitis B virus (HBV) is difficult due to HBV's genomic complexity and the need to study paired samples collected over long periods of time. In this study, serial samples were collected from eight hepatitis B virus e antigen-negative asymptomatic carriers of HBV genotype B in 1979 and 2004, thus providing a 25-year period to document the long-term molecular evolution of HBV. The rate, nature, and distribution of mutations that emerged over 25 years were determined by phylogenetic and linear regression analysis of full-length HBV genome sequences. Nucleotide hypervariability was observed within the polymerase and pre-S/S overlap region and within the core gene. The calculated mean number of nucleotide substitutions/site/year (7.9 x 10–5) was slightly higher than published estimates (1.5 x 10–5 to 5 x 10–5). Nucleotide changes in the quasispecies population did not significantly alter the molecular evolutionary rate, based on linear regression analysis of evolutionary distances among serial clone pre-S region sequences. Therefore, the directly amplified or dominant sequence was sufficient to estimate the putative molecular evolutionary rate for these long-term serial samples. On average, the ratio of synonymous (dS) to nonsynonymous (dN) substitutions was highest for the polymerase-coding region and lowest for the core-coding region. The low dS/dN ratios observed within the core suggest that selection occurs within this gene region, possibly as an immune evasion strategy. The results of this study suggest that HBV sequence divergence may occur more rapidly than previously estimated, in a host immune phase-dependent manner.

* Corresponding author. Mailing address: Public Health Agency of Canada, National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, 1015 Arlington Street, Winnipeg, Manitoba R3E 3P6, Canada. Phone: (204) 789-6061. Fax: (204) 789-2082. E-mail: carla_osiowy{at}phac-aspc.gc.ca.

Journal of Virology, November 2006, p. 10307-10314, Vol. 80, No. 21
0022-538X/06/$08.00+0     doi:10.1128/JVI.00996-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hantz, O., Parent, R., Durantel, D., Gripon, P., Guguen-Guillouzo, C., Zoulim, F. (2009). Persistence of the hepatitis B virus covalently closed circular DNA in HepaRG human hepatocyte-like cells. J. Gen. Virol. 90: 127-135 [Abstract] [Full Text]  
  • Zahn, A., Li, C., Danso, K., Candotti, D., Owusu-Ofori, S., Temple, J., Allain, J.-P. (2008). Molecular characterization of occult hepatitis B virus in genotype E-infected subjects. J. Gen. Virol. 89: 409-418 [Abstract] [Full Text]  
  • McCauley, S., de Groot, S., Mailund, T., Hein, J. (2007). Annotation of selection strengths in viral genomes. Bioinformatics 23: 2978-2986 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»