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J. Virol. doi:10.1128/JVI.01842-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Hepatitis A virus mutant spectra under the selective pressure of monoclonal antibodies: codon usage constraints limit capsid variability

Enteric Virus Laboratory, Department of Microbiology and Institute of Nutrition and Food Safety, University of Barcelona

^* To whom correspondence should be addressed. Email: abosch{at}ub.edu.

	Abstract

Severe structural constraints in the HAV capsid have been suggested as the reason for the lack of emergence of new serotypes in spite of the occurrence of complex distributions of mutants or quasispecies. The analysis of the HAV mutant spectra under the immune pressure of the monoclonal antibodies (MAb) K34C8 (immunodominant site) and H7C27 (glycophorin binding site) has revealed different evolving dynamics. Populations composed of complex ensembles of mutants with very low fitness or single dominant mutants with high fitness permit the acquisition of resistance to each of the MAbs, respectively. Deletion mutants were detected as components of the mutant spectra: up to 61 residues with an average of 19 and up to 83 residues with an average of 45 in VP3 and VP1 proteins, respectively.

A clear negative selection of those replacements affecting the residues encoded by rare codons of the capsid surface has been detected through the present quasispecies analysis, confirming certain beneficial role of such clusters. Since these clusters are located near or at the epitope regions, the need to maintain such clusters might prevent the emergence of new serotypes.