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.

Salpini, R., Piermatteo, L., Battisti, A., Colagrossi, L., Aragri, M., Yu La Rosa, K., et al. (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. VIRUSES, 12(2), 251 [10.3390/v12020251].

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

Salpini, Romina;Piermatteo, Lorenzo;Battisti, Arianna;Colagrossi, Luna;Bertoli, Ada;Saccomandi, Patrizia;Aquaro, Stefano;Angelico, Mario;Sarmati, Loredana;Andreoni, Massimo;Ceccherini-Silberstein, Francesca;Perno, Carlo Federico;Svicher, Valentina
2020-02-23

Abstract

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.
23-feb-2020
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/17 - MALATTIE INFETTIVE
English
HBV; HBV reactivation; HBsAg; N-linked glycosylation
Salpini, R., Piermatteo, L., Battisti, A., Colagrossi, L., Aragri, M., Yu La Rosa, K., et al. (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. VIRUSES, 12(2), 251 [10.3390/v12020251].
Salpini, R; Piermatteo, L; Battisti, A; Colagrossi, L; Aragri, M; Yu La Rosa, K; Bertoli, A; Saccomandi, P; Lichtner, M; Marignani, M; Maylin, S; Delaugerre, C; Morisco, F; Coppola, N; Marrone, A; Iapadre, N; Cerva, C; Aquaro, S; Angelico, M; Sarmati, L; Andreoni, M; Verheyen, J; Ceccherini-Silberstein, F; Levrero, M; Perno, Cf; Belloni, L; Svicher, V
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/233885
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 8
  • ???jsp.display-item.citation.isi??? 8
social impact