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Key mutations in the C-terminus of the HBV surface glycoprotein correlate with lower HBsAg levels in vivo, hinder HBsAg secretion in vitro and reduce HBsAg structural stability in the setting of HBeAg-negative chronic HBV genotype-D infection

Increasing evidences suggest that HBsAg-production varies across HBV-genotypes. HBsAg C-terminus plays a crucial role for HBsAg-secretion. Here, we evaluate HBsAg-levels in different HBV-genotypes in HBeAg-negative chronic infection, the correlation of specific mutations in HBsAg C-terminus with HBs...

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Published in:Emerging microbes & infections 2020-01, Vol.9 (1), p.928-939
Main Authors: Salpini, Romina, Battisti, Arianna, Piermatteo, Lorenzo, Carioti, Luca, Anastasiou, Olympia E., Gill, Upkar S., Di Carlo, Domenico, Colagrossi, Luna, Duca, Leonardo, Bertoli, Ada, La Rosa, Katia Yu, Fabeni, Lavinia, Iuvara, Alessandra, Malagnino, Vincenzo, Cerva, Carlotta, Lichtner, Miriam, Mastroianni, Claudio M., De Sanctis, Giuseppe Maria, Paoloni, Maurizio, Marignani, Massimo, Pasquazzi, Caterina, Iapadre, Nerio, Parruti, Giustino, Vecchiet, Jacopo, Sarmati, Loredana, Andreoni, Massimo, Angelico, Mario, Grelli, Sandro, T. Kennedy, Patrick, Verheyen, Jens, Aquaro, Stefano, Ceccherini-Silberstein, Francesca, Perno, Carlo Federico, Svicher, Valentina
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Language:English
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Summary:Increasing evidences suggest that HBsAg-production varies across HBV-genotypes. HBsAg C-terminus plays a crucial role for HBsAg-secretion. Here, we evaluate HBsAg-levels in different HBV-genotypes in HBeAg-negative chronic infection, the correlation of specific mutations in HBsAg C-terminus with HBsAg-levels in-vivo, their impact on HBsAg-secretion in-vitro and on structural stability in-silico. HBsAg-levels were investigated in 323 drug-naïve HBeAg-negative patients chronically infected with HBV genotype-D(N = 228), -A(N = 65) and -E(N = 30). Genotype-D was characterized by HBsAg-levels lower than genotype-A and -E (3.3[2.7-3.8]IU/ml; 3.8[3.5-4.2]IU/ml and 3.9[3.7-4.2]IU/ml, P 
ISSN:2222-1751
2222-1751
DOI:10.1080/22221751.2020.1757998