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

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 72h post-transfection 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.

Original languageEnglish
Pages (from-to)843-850
Number of pages8
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume29
Issue number4
DOIs
Publication statusPublished - 2014 Apr

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1-phenyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
Surface Antigens
Hepatitis B virus
Genome
Mutation
Hepatitis B Surface Antigens
Transfection
Chronic Hepatitis B
Virus Diseases
Staining and Labeling
Amino Acids
Immunoassay
Fluorescent Antibody Technique
Plasmids
Phenotype

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Kim, Beom Kyung ; Choi, Sung Hoon ; Ahn, Sung Hyun ; Chung, Ae Ri ; Park, Yong Kwang ; Han, Kwang Hyub ; Kim, Seungtaek ; Kim, Hyon Suk ; Park, Jeon Han ; Kim, Kyung Sik ; Lee, Hee Seung ; Cho, Yong Sang ; Kim, Kyun Hwan ; Ahn, Sang Hoon. / Pre-S mutations of hepatitis B virus affect genome replication and expression of surface antigens. In: Journal of Gastroenterology and Hepatology (Australia). 2014 ; Vol. 29, No. 4. pp. 843-850.
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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 72h post-transfection 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.",
author = "Kim, {Beom Kyung} and Choi, {Sung Hoon} and Ahn, {Sung Hyun} and Chung, {Ae Ri} and Park, {Yong Kwang} and Han, {Kwang Hyub} and Seungtaek Kim and Kim, {Hyon Suk} and Park, {Jeon Han} and Kim, {Kyung Sik} and Lee, {Hee Seung} and Cho, {Yong Sang} and Kim, {Kyun Hwan} and Ahn, {Sang Hoon}",
year = "2014",
month = "4",
doi = "10.1111/jgh.12415",
language = "English",
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Kim, BK, Choi, SH, Ahn, SH, Chung, AR, Park, YK, Han, KH, Kim, S, Kim, HS, Park, JH, Kim, KS, Lee, HS, Cho, YS, Kim, KH & Ahn, SH 2014, 'Pre-S mutations of hepatitis B virus affect genome replication and expression of surface antigens', Journal of Gastroenterology and Hepatology (Australia), vol. 29, no. 4, pp. 843-850. https://doi.org/10.1111/jgh.12415

Pre-S mutations of hepatitis B virus affect genome replication and expression of surface antigens. / Kim, Beom Kyung; Choi, Sung Hoon; Ahn, Sung Hyun; Chung, Ae Ri; Park, Yong Kwang; Han, Kwang Hyub; Kim, Seungtaek; Kim, Hyon Suk; Park, Jeon Han; Kim, Kyung Sik; Lee, Hee Seung; Cho, Yong Sang; Kim, Kyun Hwan; Ahn, Sang Hoon.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 29, No. 4, 04.2014, p. 843-850.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pre-S mutations of hepatitis B virus affect genome replication and expression of surface antigens

AU - Kim, Beom Kyung

AU - Choi, Sung Hoon

AU - Ahn, Sung Hyun

AU - Chung, Ae Ri

AU - Park, Yong Kwang

AU - Han, Kwang Hyub

AU - Kim, Seungtaek

AU - Kim, Hyon Suk

AU - Park, Jeon Han

AU - Kim, Kyung Sik

AU - Lee, Hee Seung

AU - Cho, Yong Sang

AU - Kim, Kyun Hwan

AU - Ahn, Sang Hoon

PY - 2014/4

Y1 - 2014/4

N2 - 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 72h post-transfection 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.

AB - 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 72h post-transfection 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.

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