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Journal of Virology, September 2002, p. 9516-9525, Vol. 76, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.18.9516-9525.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Molecular Evolution of Hepatitis A Virus: a New Classification Based on the Complete VP1 Protein

Mauro Costa-Mattioli,1,2 Juan Cristina,2 Héctor Romero,3 Raoul Perez-Bercof,4 Didier Casane,5 Rodney Colina,2 Laura Garcia,2 Ines Vega,6 Graciela Glikman,7 Victor Romanowsky,7 Alejandro Castello,7 Elisabeth Nicand,8 Michelle Gassin,1 Sylviane Billaudel,1 and Virginie Ferré1*

Laboratorie de Virologie UPRES-EA1156, Institut de Biologie, Centre Hospitalier Regional Universitaire de Nantes, 44093 Nantes,1 Laboratoire de Génétique des Virus CNRS, 91198 Gif-sur-Yvette,4 Phylogenie, Bioinformatique et Genome, CNRS, Universite Pierre et Marie Curie, 75005 Paris,5 Laboratoire de Biologie Clinique, HIA Val-de GrÂce, 75230 Paris, France,8 Departamento de Técnicas Nucleares Aplicadas, Centro de Investigaciones Nucleares,2 Laboratorio de Organización y Evolución del Genoma, Instituto de Biología, Facultad de Ciencias, Universidad de la República, 11400 Montevideo, Uruguay,3 Instituto de Hematologia, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile,6 Department of Science and Technology, Universidad Nacional de Quilmes, Buenos Aires, Argentina7

Received 11 March 2002/ Accepted 20 June 2002

Hepatitis A virus (HAV) is a positive-stranded RNA virus in the genus Hepatovirus in the family Picornaviridae. So far, analysis of the genetic variability of HAV has been based on two discrete regions, the VP1/2A junction and the VP1 N terminus. In this report, we determined the nucleotide and deduced amino acid sequences of the complete VP1 gene of 81 strains from France, Kosovo, Mexico, Argentina, Chile, and Uruguay and compared them with the sequences of seven strains of HAV isolated elsewhere. Overall strain variation in the complete VP1 gene was found to be as high as 23.7% at the nucleotide level and 10.5% at the amino acid level. Different phylogenetic methods revealed that HAV sequences form five distinct and well-supported genetic lineages. Within these lineages, HAV sequences clustered by geographical origin only for European strains. The analysis of the complete VP1 gene allowed insight into the mode of evolution of HAV and revealed the emergence of a novel variant with a 15-amino-acid deletion located on the VP1 region where neutralization escape mutations were found. This could be the first antigenic variant of HAV so far identified.

* Corresponding author. Mailing address: Laboratoire de Virologie, Institut de Biologie, CHU Nantes, Nantes, France. Phone: 33 02 40 08 41 01. Fax: 33 02 40 08 41 39. E-mail: vferre{at}chu-nantes.fr.

Journal of Virology, September 2002, p. 9516-9525, Vol. 76, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.18.9516-9525.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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