title: A single mutation in the glycophorin A binding site of hepatitis A virus enhances virus clearance from the blood and results in a lower fitness variant.
abstract: Hepatitis A virus (HAV) has previously been reported to bind to human red blood cells through interaction with glycophorin A. Residue K221 of VP1 and the surrounding VP3 residues are involved in such an interaction. This capsid region is specifically recognized by the monoclonal antibody H7C27. A monoclonal antibody-resistant mutant with the mutation G1217D has been isolated. In the present study, the G1217D mutant was characterized physically and biologically in comparison with the parental HM175 43c strain. The G1217D mutant is more sensitive to acid pH and binds more efficiently to human and rat erythrocytes than the parental 43c strain. In a rat model, it is eliminated from serum more rapidly and consequently reaches the liver with a certain delay compared to the parental 43c strain. In competition experiments performed in vivo in the rat model, the G1217D mutant was efficiently outcompeted by the parental 43c strain. Only in the presence of antibodies reacting specifically with the parental 43c strain could the G1217D mutant outcompete the parental 43c strain in serum, although the latter still showed a remarkable ability to reach the liver. Altogether, these results indicate that the G1217D mutation induces a low fitness phenotype which could explain the lack of natural antigenic variants of the glycophorin A binding site.
authors.affiliation: Enteric Virus Laboratory, University of Barcelona, Barcelona, Spain.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Costafreda
authors.forename: Enric
authors.initials: E
authors.lastname: Ribes
authors.forename: Angels
authors.initials: A
authors.lastname: Franch
authors.forename: Albert
authors.initials: A
authors.lastname: Bosch
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Pintó
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D004912:Erythrocytes / Q000378:metabolism* / Q000821:virology; D005260:Female; D006021:Glycophorins / Q000235:genetics / Q000378:metabolism*; D030041:Hepatitis A virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020125:Mutation, Missense; D051381:Rats; D017208:Rats, Wistar
chemical_list: D006021:Glycophorins