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Pre-S mutations of hepatitis B virus affect genome replication and expression of surface antigens

Authors
 Beom Kyung Kim  ;  Sung Hoon Choi  ;  Sung Hyun Ahn  ;  Ae Ri Chung  ;  Yong Kwang Park  ;  Kwang-Hyub Han  ;  Seungtaek Kim  ;  Hyon-Suk Kim  ;  Jeon Han Park  ;  Kyung Sik Kim  ;  Hee Seung Lee  ;  Yong Sang Cho  ;  Kyun-Hwan Kim  ;  Sang Hoon Ahn 
Citation
 JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Vol.29(4) : 843-850, 2014 
Journal Title
 JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 
ISSN
 0815-9319 
Issue Date
2014
Keywords
Edema ; Pioglitazone
Abstract
BACKGROUNDS AND AIMS: In chronic hepatitis B virus (HBV) infection, quantitative HBV surface antigen (qHBsAg) is useful for monitoring viral replication and treatment responses. We aimed to determine whether pre-S mutations have any effect on circulating qHBsAg. METHODS: Plasmids expressing 1–8 amino acid deletion in pre-S1 ("pre-S1Δ1-8") and 3-25 amino acid deletion in pre-S2 ("pre-S2Δ3-25") were constructed. At 72 h posttransfection into Huh7 cells, qHBsAg were measured using electrochemiluminescence immunoassay analyzer. To mimic milieus of quasispecies, we co-transfected either pre-S1Δ1-8 or pre-S2Δ3-25 with wild type (WT). RESULTS: Pre-S mutations affected transcription and replication ability of HBV because of altered overlapping polymerase. Compared with WT, extracellular qHBsAg in pre-S1Δ1-8 and pre-S2Δ3-25 were on average 3.87-fold higher and 0.92-fold lower, respectively, whereas intracellular qHBsAg in pre-S1Δ1-8 and pre-S2Δ3-25 were 0.57-fold lower and 1.60-fold higher, respectively. Immunofluorescence staining of cellular HBsAg showed that pre-S1Δ1-8 had less staining and that pre-S2Δ3-25 had denser staining. As ratios of either pre-S1Δ1-8 or pre-S2Δ3-25:WT increased from 0:10 to 10:0 gradually, relative extracellular qHBsAg increased from 1.0 to 3.85 in pre-S1Δ1-8 co-transfection, whereas those decreased from 1.0 to 0.88 in pre-S2Δ3-25 co-transfection. CONCLUSION: Pre-S mutations exhibit different phenotypes of genome replication and HBsAg expression according to their locations. Thus, qHBsAg level for diagnosis and prognostification in chronic HBV infection should be used more cautiously, considering emergences of pre-S deletion mutants.
Full Text
http://onlinelibrary.wiley.com/doi/10.1111/jgh.12415/abstract
DOI
10.1111/jgh.12415
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sik(김경식) ORCID logo https://orcid.org/0000-0001-9498-284X
Kim, Beom Kyung(김범경) ORCID logo https://orcid.org/0000-0002-5363-2496
Kim, Seung Taek(김승택)
Kim, Hyon Suk(김현숙) ORCID logo https://orcid.org/0000-0001-5662-7740
Park, Jeon Han(박전한) ORCID logo https://orcid.org/0000-0001-9604-3205
Ahn, Sang Hoon(안상훈) ORCID logo https://orcid.org/0000-0002-3629-4624
Lee, Hee Seung(이희승) ORCID logo https://orcid.org/0000-0002-2825-3160
Chung, Ae Ri(정애리)
Choi, Sung Hoon(최성훈)
Han, Kwang-Hyub(한광협) ORCID logo https://orcid.org/0000-0003-3960-6539
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/98932
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