A Hyper-Glycosylation of HBV Surface Antigen Correlates with HBsAg-Negativity at Immunosuppression-Driven HBV Reactivation in Vivo and Hinders HBsAg Recognition In Vitro - CRCL-Epigénetique et épigénomique des carcinomes viro-induits Accéder directement au contenu
Article Dans Une Revue Viruses Année : 2020

A Hyper-Glycosylation of HBV Surface Antigen Correlates with HBsAg-Negativity at Immunosuppression-Driven HBV Reactivation in Vivo and Hinders HBsAg Recognition In Vitro

Romina Salpini
Lorenzo Piermatteo
Arianna Battisti
  • Fonction : Auteur
Luna Colagrossi
  • Fonction : Auteur
Marianna Aragri
  • Fonction : Auteur
Katia Yu La Rosa
  • Fonction : Auteur
Ada Bertoli
  • Fonction : Auteur
Patrizia Saccomandi
  • Fonction : Auteur
Miriam Lichtner
  • Fonction : Auteur
Massimo Marignani
  • Fonction : Auteur
Sarah Maylin
  • Fonction : Auteur
Constance Delaugerre
  • Fonction : Auteur
Filomena Morisco
  • Fonction : Auteur
Nicola Coppola
Aldo Marrone
  • Fonction : Auteur
Nerio Iapadre
  • Fonction : Auteur
Carlotta Cerva
  • Fonction : Auteur
Stefano Aquaro
Mario Angelico
  • Fonction : Auteur
Loredana Sarmati
Massimo Andreoni
  • Fonction : Auteur
Jens Verheyen
  • Fonction : Auteur
Carlo Federico Perno
  • Fonction : Auteur
Laura Belloni
  • Fonction : Auteur
Valentina Svicher
  • Fonction : Auteur

Résumé

Immune-suppression driven Hepatitis B Virus (HBV)-reactivation poses serious concerns since it occurs in several clinical settings and can result in severe forms of hepatitis. Previous studies showed that HBV strains, circulating in patients with HBV-reactivation, are characterized by an enrichment of immune-escape mutations in HBV surface antigen (HBsAg). Here, we focused on specific immune-escape mutations associated with the acquisition of N-linked glycosylation sites in HBsAg (NLGSs). In particular, we investigated profiles of NLGSs in 47 patients with immunosuppression-driven HBV-reactivation and we evaluated their impact on HBsAg-antigenicity and HBV-replication in vitro. At HBV-reactivation, despite a median serum HBV-DNA of 6.7 [5.3–8.0] logIU/mL, 23.4% of patients remained HBsAg-negative. HBsAg-negativity at HBV-reactivation correlated with the presence of >1 additional NLGSs (p < 0.001). These NLGSs are located in the major hydrophilic region of HBsAg (known to be the target of antibodies) and resulted from the single mutation T115N, T117N, T123N, N114ins, and from the triple mutant S113N+T131N+M133T. In vitro, NLGSs strongly alter HBsAg antigenic properties and recognition by antibodies used in assays for HBsAg-quantification without affecting HBsAg-secretion and other parameters of HBV-replication. In conclusion, additional NLGSs correlate with HBsAg-negativity despite HBV-reactivation, and hamper HBsAg-antigenicity in vitro, supporting the role of NGSs in immune-escape and the importance of HBV-DNA for a proper diagnosis of HBV-reactivation.

Dates et versions

hal-03851002 , version 1 (14-11-2022)

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Citer

Romina Salpini, Lorenzo Piermatteo, Arianna Battisti, Luna Colagrossi, Marianna Aragri, et al.. A Hyper-Glycosylation of HBV Surface Antigen Correlates with HBsAg-Negativity at Immunosuppression-Driven HBV Reactivation in Vivo and Hinders HBsAg Recognition In Vitro. Viruses, 2020, 12 (2), pp.251. ⟨10.3390/v12020251⟩. ⟨hal-03851002⟩
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