(HAV) is a hepatotropic member of the family . Despite a remarkable antigenic stability, recent results have shown that HAV exists and in cell culture as distributions of genetically related, non-identical variants, referred to as quasispecies. To gain insight into HAV evolution over time in a specific geographical region, genotype I consensus sequences from strains isolated in France in consecutive years were studied. Phylogenetic neighbour-joining method and a non-hierarchical partition analysis, designed to analyse viral quasispecies, indicate that at least five distinct subpopulations of HAV were identified in the course of the disease episode. Strikingly, over time, different subpopulations cycled in dominance. The coexistence of distinct subpopulations whose frequency varies with time is consistent with quasispecies dynamics, and suggests that variation in the dominant HAV population may provide HAV adaptability without being reflected in significant antigenic variation.


Article metrics loading...

Loading full text...

Full text loading...



  1. Agol, V. A. ( 2002; ). Picornavirus genome: an overview. In Molecular Biology of Picornaviruses, pp. 127–148. Edited by B. Semler & E. Wimmer. Washington, DC: ASM Press.
  2. Baccam, P., Thompson, R. J., Fedrigo, O., Carpenter, S. & Cornette, J. L. ( 2001; ). PAQ: partition analysis of quasispecies. Bioinformatics 17, 16–22.[CrossRef]
    [Google Scholar]
  3. Baccam, P., Thompson, R. J., Li, Y. & 7 other authors ( 2003; ). Subpopulations of equine infectious anemia virus Rev coexist in vivo and differ in phenotype. J Virol 77, 12122–12131.[CrossRef]
    [Google Scholar]
  4. Costa-Mattioli, M., Cristina, J., Romero, H. & 12 other authors ( 2002; ). Molecular evolution of hepatitis A virus: a new classification based on the complete VP1 protein. J Virol 76, 9516–9525.[CrossRef]
    [Google Scholar]
  5. Costa-Mattioli, M., Ferre, V., Casane, D. & 7 other authors ( 2003; ). Evidence of recombination in natural populations of hepatitis A virus. Virology 311, 51–59.[CrossRef]
    [Google Scholar]
  6. Domingo, E., Biebricher, C., Eigen, M. & Holland, J. J. ( 2001; ). Quasispecies and RNA Virus Evolution: Principles and Consequences. Austin, TX: Landes Bioscience.
  7. Felsenstein, J. ( 1993; ). phylip (phylogeny inference package) version 3.572c. Department of Genome Sciences, University of Washington, Seattle, USA.
  8. Kumar, S., Tamura, K. & Nei, M. ( 1994; ). mega: molecular evolutionary genetics analysis software for microcomputers. Comput Appl Biosci 10, 189–191.
    [Google Scholar]
  9. Palmenberg, A. C. ( 1989; ). Sequence alignments of picornaviral capsid proteins. In Molecular Aspects of Picornaviral Infection and Detection. Edited by B. L. Semler & E. Ehenfeld. Washington, DC: American Society for Microbiology.
  10. Papathanasopoulos, M. A., Hunt, G. M. & Tiemessen, C. T. ( 2003; ). Evolution and diversity of HIV-1 in Africa – a review. Virus Genes 26, 151–163.[CrossRef]
    [Google Scholar]
  11. Robertson, B. H., Jansen, R. W., Khanna, B. & 10 other authors ( 1992; ). Genetic relatedness of hepatitis A virus strains recovered from different geographical regions. J Gen Virol 73, 1365–1377.[CrossRef]
    [Google Scholar]
  12. Saitou, N. & Nei, M. ( 1987; ). The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4, 406–425.
    [Google Scholar]
  13. Sanchez, G., Bosch, A., Gomez-Mariano, G., Domingo, E. & Pinto, R. M. ( 2003a; ). Evidence for quasispecies distributions in the human hepatitis A virus genome. Virology 315, 34–42.[CrossRef]
    [Google Scholar]
  14. Sanchez, G., Bosch, A. & Pinto, R. M. ( 2003b; ). Genome variability and capsid structural constraints of hepatitis A virus. J Virol 77, 452–459.[CrossRef]
    [Google Scholar]
  15. Shapshak, P., Segan, D. M., Crandall, K. A. & 7 other authors ( 1999; ). Independent evolution of HIV type 1 in different brain regions. AIDS Res Hum Retroviruses 15, 811–820.[CrossRef]
    [Google Scholar]
  16. Sneath, P. H. A. & Sokal, R. R. ( 1973; ). Numerical Taxonomy. San Francisco: Freeman.
  17. Swofford, D. L. ( 1999; ). paup*. Phylogenetic Analysis Using Parsimony (and Other methods), version 4. Sunderland, MA: Sinauer Associates.
  18. Thompson, J. D., Higgins, D. G. & Gibson, T. J. ( 1994; ). clustal w: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22, 4673–4680.[CrossRef]
    [Google Scholar]
  19. Ticehurst, J., Cohen, J. I., Feinstone, S. M., Purcell, R. H., Jansen, R. W. & Lemon, S. M. ( 1989; ). Replication of hepatitis A virus: new ideas from studies with cloned cDNA. In Molecular Aspects of Picornaviral Infection and Detection, pp. 27–50. Edited by B. L. Semler & E. Ehenfeld. Washington, DC: American Society for Microbiology.
  20. Van Regenmortel, M. H. V. ( 2000; ). In Virus Taxonomy. Seventh Report of the International Committee on Taxonomy of Viruses. Edited by M. H. V. van Regenmortel, C. M. Fauquet, D. H. L. Bishop, E. B. Carstens, M. K. Estes, S. M. Lemon, J. Maniloff, M. A. Mayo, D. J. McGeoch, C. R. Pringle & R. B. Wickner. San Diego: Academic Press.
  21. Wimmer, E. & Murdin, A. ( 1991; ). Hepatitis A and the molecular biology of picornaviruses: a case for a new genus of the family Picornaviridae. In Viral Hepatitis and Liver Disease, pp. 1–41. Edited by F. B. Hollinger, S. M. Lemon & H. S. Margolis. Baltimore: Williams & Wilkins.

Data & Media loading...


vol. , part 1, pp. 115 - 118

Phylogenetic analysis of the complete VP1 region using p-distance model and the UPGMA method

French HAV strains examined in this study

[Single PDF file](345 KB)


Most cited this month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error