Journal article

Publication year: 2023

Journal: Viruses

Volume number: 15

Issue number: 4

eISSN: 1999-4915

Open access status: Gold

DOI Link: https://doi.org/10.3390/v15040838

Publisher: MDPI

Abstract: 
Chronic hepatitis B virus (HBV) infection is a global health threat. Mutations in the surface antigen of HBV (HBsAg) may alter its antigenicity, infectivity, and transmissibility. A patient positive for HBV DNA and detectable but low-level HBsAg in parallel with anti-HBs suggested the presence of immune and/or diagnostic escape variants. To support this hypothesis, serum-derived HBs gene sequences were amplified and cloned for sequencing, which revealed infection with exclusively non-wildtype HBV subgenotype (sgt) D3. Three distinct mutations in the antigenic loop of HBsAg that caused additional N-glycosylation were found in the variant sequences, including a previously undescribed six-nucleotide insertion. Cellular and secreted HBsAg was analyzed for N-glycosylation in Western blot after expression in human hepatoma cells. Secreted HBsAg was also subjected to four widely used, state-of-the-art diagnostic assays, which all failed to detect the hyperglycosylated insertion variant. Additionally, the recognition of mutant HBsAg by vaccine- and natural infection-induced anti-HBs antibodies was severely impaired. Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity.

Harvard Citation style: Lehmann, F., Slanina, H., Roderfeld, M., Roeb, E., Trebicka, J., Ziebuhr, J., et al. (2023) A Novel Insertion in the Hepatitis B Virus Surface Protein Leading to Hyperglycosylation Causes Diagnostic and Immune Escape, Viruses, 15(4), Article 838. https://doi.org/10.3390/v15040838

APA Citation style: Lehmann, F., Slanina, H., Roderfeld, M., Roeb, E., Trebicka, J., Ziebuhr, J., Gerlich, W., Schuettler, C., Schlevogt, B., & Glebe, D. (2023). A Novel Insertion in the Hepatitis B Virus Surface Protein Leading to Hyperglycosylation Causes Diagnostic and Immune Escape. Viruses. 15(4), Article 838. https://doi.org/10.3390/v15040838