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

Filomena Morisco¹  Arianna Battisti²  Francesca Ceccherini-Silberstein²  Lorenzo Piermatteo²  Marianna Aragri²  Luna Colagrossi²  Katia Yu La Rosa²  Romina Salpini²  Ada Bertoli²  Valentina Svicher²  Patrizia Saccomandi²  Massimo Marignani³  Laura Belloni⁴  Massimo Levrero⁴  Nicola Coppola⁵  CarloFederico Perno⁶  Stefano Aquaro⁷  Mario Angelico⁸  Nerio Iapadre⁹  Carlotta Cerva^1,10  Loredana Sarmati^1,10  Massimo Andreoni^1,10  Jens Verheyen^1,11  Aldo Marrone^1,12  Constance Delaugerre^1,13  Sarah Maylin^1,13  Miriam Lichtner^1,14 

[1] Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80138 Naples, Italy;Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy;Department of Gastroenterology, S.Andrea Hospital, 00189 Rome, Italy;Department of Internal Medicine-DMISM, Sapienza University, 00185 Rome, Italy;Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80138 Naples, Italy;Department of Oncology and Haemato-oncology, University of Milan, 20122 Milan, Italy;Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy;Hepatology Unit, Tor Vergata University Hospital, 00133 Rome, Italy;Infectious Diseases Unit, San Salvatore Hospital, 67100 L’Aquila, Italy;Infectious Diseases Unit, Tor Vergata University Hospital, 00133 Rome, Italy;Institute of Virology, University-Hospital, University Duisburg-Essen, 47057 Essen, Germany;Internal Medicine and Hepatology Unit, Second University of Naples, 80138 Naples, Italy;Laboratoire de Virologie, AP-HP Hopital Saint-Louis, 75010 Paris, France;Public Health and Infectious Disease Department, Sapienza University, 00185 Rome, Italy;

关键词: hbv;    hbv reactivation;    hbsag;    n-linked glycosylation;   

DOI  :  10.3390/v12020251

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown