A Hyper-Glycosylation of HBV Surface Antigen Correlates with HBsAg-Negativity at Immunosuppression-Driven HBV Reactivation in Vivo and Hinders HBsAg Recognition In Vitro
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-02-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/2/251 |
| id |
doaj-c5b283c6909746d78c72accaa56e6b15 |
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| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Romina Salpini Lorenzo Piermatteo Arianna Battisti Luna Colagrossi Marianna Aragri Katia Yu La Rosa Ada Bertoli Patrizia Saccomandi Miriam Lichtner Massimo Marignani Sarah Maylin Constance Delaugerre Filomena Morisco Nicola Coppola Aldo Marrone Nerio Iapadre Carlotta Cerva Stefano Aquaro Mario Angelico Loredana Sarmati Massimo Andreoni Jens Verheyen Francesca Ceccherini-Silberstein Massimo Levrero Carlo Federico Perno Laura Belloni Valentina Svicher |
| spellingShingle |
Romina Salpini Lorenzo Piermatteo Arianna Battisti Luna Colagrossi Marianna Aragri Katia Yu La Rosa Ada Bertoli Patrizia Saccomandi Miriam Lichtner Massimo Marignani Sarah Maylin Constance Delaugerre Filomena Morisco Nicola Coppola Aldo Marrone Nerio Iapadre Carlotta Cerva Stefano Aquaro Mario Angelico Loredana Sarmati Massimo Andreoni Jens Verheyen Francesca Ceccherini-Silberstein Massimo Levrero Carlo Federico Perno Laura Belloni Valentina Svicher 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 hbv hbv reactivation hbsag n-linked glycosylation |
| author_facet |
Romina Salpini Lorenzo Piermatteo Arianna Battisti Luna Colagrossi Marianna Aragri Katia Yu La Rosa Ada Bertoli Patrizia Saccomandi Miriam Lichtner Massimo Marignani Sarah Maylin Constance Delaugerre Filomena Morisco Nicola Coppola Aldo Marrone Nerio Iapadre Carlotta Cerva Stefano Aquaro Mario Angelico Loredana Sarmati Massimo Andreoni Jens Verheyen Francesca Ceccherini-Silberstein Massimo Levrero Carlo Federico Perno Laura Belloni Valentina Svicher |
| author_sort |
Romina Salpini |
| title |
A Hyper-Glycosylation of HBV Surface Antigen Correlates with HBsAg-Negativity at Immunosuppression-Driven HBV Reactivation in Vivo and Hinders HBsAg Recognition In Vitro |
| title_short |
A Hyper-Glycosylation of HBV Surface Antigen Correlates with HBsAg-Negativity at Immunosuppression-Driven HBV Reactivation in Vivo and Hinders HBsAg Recognition In Vitro |
| title_full |
A Hyper-Glycosylation of HBV Surface Antigen Correlates with HBsAg-Negativity at Immunosuppression-Driven HBV Reactivation in Vivo and Hinders HBsAg Recognition In Vitro |
| title_fullStr |
A Hyper-Glycosylation of HBV Surface Antigen Correlates with HBsAg-Negativity at Immunosuppression-Driven HBV Reactivation in Vivo and Hinders HBsAg Recognition In Vitro |
| title_full_unstemmed |
A Hyper-Glycosylation of HBV Surface Antigen Correlates with HBsAg-Negativity at Immunosuppression-Driven HBV Reactivation in Vivo and Hinders HBsAg Recognition In Vitro |
| title_sort |
hyper-glycosylation of hbv surface antigen correlates with hbsag-negativity at immunosuppression-driven hbv reactivation in vivo and hinders hbsag recognition in vitro |
| publisher |
MDPI AG |
| series |
Viruses |
| issn |
1999-4915 |
| publishDate |
2020-02-01 |
| description |
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 (<i>p</i> < 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. |
| topic |
hbv hbv reactivation hbsag n-linked glycosylation |
| url |
https://www.mdpi.com/1999-4915/12/2/251 |
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| _version_ |
1724892124941385728 |
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doaj-c5b283c6909746d78c72accaa56e6b152020-11-25T02:16:11ZengMDPI AGViruses1999-49152020-02-0112225110.3390/v12020251v12020251A Hyper-Glycosylation of HBV Surface Antigen Correlates with HBsAg-Negativity at Immunosuppression-Driven HBV Reactivation in Vivo and Hinders HBsAg Recognition In VitroRomina Salpini0Lorenzo Piermatteo1Arianna Battisti2Luna Colagrossi3Marianna Aragri4Katia Yu La Rosa5Ada Bertoli6Patrizia Saccomandi7Miriam Lichtner8Massimo Marignani9Sarah Maylin10Constance Delaugerre11Filomena Morisco12Nicola Coppola13Aldo Marrone14Nerio Iapadre15Carlotta Cerva16Stefano Aquaro17Mario Angelico18Loredana Sarmati19Massimo Andreoni20Jens Verheyen21Francesca Ceccherini-Silberstein22Massimo Levrero23Carlo Federico Perno24Laura Belloni25Valentina Svicher26Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyPublic Health and Infectious Disease Department, Sapienza University, 00185 Rome, ItalyDepartment of Gastroenterology, S.Andrea Hospital, 00189 Rome, ItalyLaboratoire de Virologie, AP-HP Hopital Saint-Louis, 75010 Paris, FranceLaboratoire de Virologie, AP-HP Hopital Saint-Louis, 75010 Paris, FranceDepartment of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80138 Naples, ItalyDepartment of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80138 Naples, ItalyInternal Medicine and Hepatology Unit, Second University of Naples, 80138 Naples, ItalyInfectious Diseases Unit, San Salvatore Hospital, 67100 L’Aquila, ItalyInfectious Diseases Unit, Tor Vergata University Hospital, 00133 Rome, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyHepatology Unit, Tor Vergata University Hospital, 00133 Rome, ItalyInfectious Diseases Unit, Tor Vergata University Hospital, 00133 Rome, ItalyInfectious Diseases Unit, Tor Vergata University Hospital, 00133 Rome, ItalyInstitute of Virology, University-Hospital, University Duisburg-Essen, 47057 Essen, GermanyDepartment of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Internal Medicine-DMISM, Sapienza University, 00185 Rome, ItalyDepartment of Oncology and Haemato-oncology, University of Milan, 20122 Milan, ItalyDepartment of Internal Medicine-DMISM, Sapienza University, 00185 Rome, ItalyDepartment of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyImmune-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 (<i>p</i> < 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.https://www.mdpi.com/1999-4915/12/2/251hbvhbv reactivationhbsagn-linked glycosylation |