Abstract
Hepatitis B surface antigen (HBsAg) promotes persistent hepatitis B virus (HBV) infection. It primarily corresponds to small (S) envelope protein secreted as subviral particles. We previously found that genotype D clones expressed less S protein than genotype A clones but showed higher extracellular/intracellular ratio of HBsAg suggesting more efficient secretion. The current study aimed to characterize the underlying mechanism(s) by comparing a subgenotype A2 clone (geno5.4) with a subgenotype D2 clone (geno1.2). Five types of full-length or subgenomic constructs were transfected to Huh7 cells at different dosage. HBsAg was quantified by enzyme linked immunosorbent assay while envelope proteins were detected by Western blot. We found that ratio of extracellular/intracellular HBsAg decreased at increasing amounts of DNA transfected. Conflicting findings from two types of subgenomic construct confirmed stronger secretion inhibitory effect of the genotype D-derived large envelope protein. Chimeric constructs followed by site-directed mutagenesis revealed geno1.2 specific V118/T127 and F161/A168 in the S protein as promoting and inhibitory of HBsAg secretion, respectively. In conclusion, more efficient HBsAg secretion by subgenotype D2 than subgenotype A2 is attributed to lower level of S protein expression in addition to V118 and T127 in S protein, although its F161 and A168 sequences rather reduce HBsAg secretion.
Highlights
Chronic infection with hepatitis B virus (HBV) is a leading cause of liver cirrhosis and hepatocellular carcinoma
It can transcribe all the HBV RNAs leading to genome replication, envelope protein expression, and hepatitis B surface antigen (HBsAg) secretion
Since the divergent residues 10 and 12 correspond to positions 118 and 127 in S protein, respectively, these findings suggested that V118 and T127 in the S protein of geno1.2 promoted HBsAg secretion relative to T118 and P127 found in geno5.4
Summary
Chronic infection with hepatitis B virus (HBV) is a leading cause of liver cirrhosis and hepatocellular carcinoma. According to divergence of their genomic sequences, HBV isolates worldwide can be classified into genotypes A–J. Genotypes B and C predominate in East Asia and are often transmitted vertically from infected mothers. Genotypes A and D co-circulate in many other parts of the world and are transmitted mostly in adulthood through sex, blood transfusion, or shared needles. Viruses 2020, 12, 967 markers of ongoing HBV infection include hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg). HBeAg is a secreted soluble version of core antigen, the building block of core particle (capsid) that shields the viral genome. It was initially identified as the “Australia antigen” [1]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
