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Article Dans Une Revue Archives of Virology Année : 2015

Characterization of C69R variant HBsAg: effect on binding to anti-HBs and the structure of virus-like particles

Nadia Hadiji-Abbes
  • Fonction : Auteur
Wafa Mihoubi
  • Fonction : Auteur
Marta Martin Fernandez
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Carole Karakasyan-Dia
  • Fonction : Auteur
Fakher Frikha
  • Fonction : Auteur
Csilla Gergely
Thierry Jouenne
Raja Mokdad-Gargouri
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  • PersonId : 858314

Résumé

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.
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Dates et versions

hal-01179792 , version 1 (23-07-2015)

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Nadia Hadiji-Abbes, Wafa Mihoubi, Marta Martin Fernandez, Carole Karakasyan-Dia, Fakher Frikha, et al.. Characterization of C69R variant HBsAg: effect on binding to anti-HBs and the structure of virus-like particles. Archives of Virology, 2015, pp.10.1007/s00705-015-2515-y. ⟨10.1007/s00705-015-2515-y⟩. ⟨hal-01179792⟩
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