In:
Journal of Gastroenterology and Hepatology, Wiley, Vol. 29, No. 4 ( 2014-04), p. 843-850
Abstract:
In chronic hepatitis B virus ( HBV ) infection, quantitative HBV surface antigen (q HB s A g) is useful for monitoring viral replication and treatment responses. We aimed to determine whether pre‐ S mutations have any effect on circulating q HB s A g. Methods Plasmids expressing 1–8 amino acid deletion in pre‐ S 1 (“pre‐ S 1Δ1‐8”) and 3‐25 amino acid deletion in pre‐ S 2 (“pre‐ S 2Δ3‐25”) were constructed. At 72 h post‐transfection into H uh7 cells, q HB s A g were measured using electrochemiluminescence immunoassay analyzer. To mimic milieus of quasispecies, we co‐transfected either pre‐ S 1Δ1‐8 or pre‐ S 2Δ3‐25 with wild type ( WT ). Results Pre‐ S mutations affected transcription and replication ability of HBV because of altered overlapping polymerase. Compared with WT , extracellular q HB s A g in pre‐ S 1Δ1‐8 and pre‐ S 2Δ3‐25 were on average 3.87‐fold higher and 0.92‐fold lower, respectively, whereas intracellular q HB s A g in pre‐ S 1Δ1‐8 and pre‐ S 2Δ3‐25 were 0.57‐fold lower and 1.60‐fold higher, respectively. Immunofluorescence staining of cellular HB s A g showed that pre‐ S 1Δ1‐8 had less staining and that pre‐ S 2Δ3‐25 had denser staining. As ratios of either pre‐ S 1Δ1‐8 or pre‐ S 2Δ3‐25: WT increased from 0:10 to 10:0 gradually, relative extracellular q HB s A g increased from 1.0 to 3.85 in pre‐ S 1Δ1‐8 co‐transfection, whereas those decreased from 1.0 to 0.88 in pre‐ S 2Δ3‐25 co‐transfection. Conclusion Pre‐ S mutations exhibit different phenotypes of genome replication and HB s A g expression according to their locations. Thus, q HB s A g level for diagnosis and prognostification in chronic HBV infection should be used more cautiously, considering emergences of pre‐ S deletion mutants.
Type of Medium:
Online Resource
ISSN:
0815-9319
,
1440-1746
DOI:
10.1111/jgh.2014.29.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2006782-3
