%0 Journal Article
%T Characterization of C69R variant HBsAg: effect on binding to anti-HBs and the structure of virus-like particles
%+ Laboratoire Charles Coulomb (L2C)
%+ Polymères Biopolymères Surfaces (PBS)
%+ Centre de Biotechnologie de Sfax (CBS)
%A Hadiji-Abbes, Nadia
%A Mihoubi, Wafa
%A Martin Fernandez, Marta
%A Karakasyan-Dia, Carole
%A Frikha, Fakher
%A Gergely, Csilla
%A Jouenne, Thierry
%A Gargouri, Ali
%A Mokdad-Gargouri, Raja
%< avec comité de lecture
%@ 0304-8608
%J Archives of Virology
%I Springer Verlag
%P 10.1007/s00705-015-2515-y
%8 2015-07-15
%D 2015
%R 10.1007/s00705-015-2515-y
%Z Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph]Journal articles
%X Several variants of the major ‘‘a’’ determinant of the HBsAg, the main target of HBV neutralization by antibodies, have been described. However, mutations out- side this region have not been as thoroughly investigated. During the genotyping of HBV from Tunisian patients with chronic hepatitis B, we identified a variant with a C69R substitution in the cytosolic loop of the S protein, resulting in a change in the hydrophobicity profile compared to the wild-type HBsAg. Wild-type and mutant HBsAgs were produced in Saccharomyces cerevisiae and recombinant proteins were tested for their ability to correctly self- assemble into virus-like particles (VLPs), and their ability to bind to HBs antibodies. The C69R substitution resulted in a decrease in binding to commercial anti-HBs antibod- ies, and although the variant appeared to assemble properly into VLPs, the average size of the particles was larger than that of the wild-type HBsAg. Prediction of the tertiary structure of the C69R mutant revealed a change in the first (aa 60-70) and the second loop (aa 110 to 120) compared to the wild-type protein. Furthermore, we showed by an isothermal titration calorimetry assay that the interaction between the wild-type HBsAg and the anti-HBs antibody was exothermic, whereas that with the mutant C69R was endothermic, indicating an effect on the binding affinity.
%G English
%L hal-01179792
%U https://hal.science/hal-01179792
%~ CNRS
%~ INSA-ROUEN
%~ L2C
%~ COMUE-NORMANDIE
%~ INC-CNRS
%~ MIPS
%~ UNIV-MONTPELLIER
%~ UNIROUEN
%~ ENSICAEN
%~ UNILEHAVRE
%~ UNICAEN
%~ INSA-GROUPE
%~ PBS
%~ UM-2015-2021
%~ TEST2-HALCNRS