Pre-S mutations of hepatitis B virus affect genome replication and expression of surface antigens
Beom Kyung Kim
Deparment of Internal medicine, Yonsei University College of Medicine, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Liver Cirrhosis Clinical Research Center, Seoul, Korea
Search for more papers by this authorSung Hoon Choi
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Liver Cirrhosis Clinical Research Center, Seoul, Korea
Search for more papers by this authorSung Hyun Ahn
Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, Konkuk University School of Medicine, Seoul, Korea
Search for more papers by this authorAe Ri Chung
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Liver Cirrhosis Clinical Research Center, Seoul, Korea
Search for more papers by this authorYong Kwang Park
Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, Konkuk University School of Medicine, Seoul, Korea
Search for more papers by this authorKwang-Hyub Han
Deparment of Internal medicine, Yonsei University College of Medicine, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Liver Cirrhosis Clinical Research Center, Seoul, Korea
Search for more papers by this authorSeungtaek Kim
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Liver Cirrhosis Clinical Research Center, Seoul, Korea
Search for more papers by this authorHyon-Suk Kim
Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorJeon Han Park
Department of Microbiology, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorKyung Sik Kim
Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorHee Seung Lee
Deparment of Internal medicine, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorYong Sang Cho
College of Global General Education, Gachon University, Seongnam-si, Korea
Search for more papers by this authorKyun-Hwan Kim
Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, Konkuk University School of Medicine, Seoul, Korea
Search for more papers by this authorCorresponding Author
Sang Hoon Ahn
Deparment of Internal medicine, Yonsei University College of Medicine, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Liver Cirrhosis Clinical Research Center, Seoul, Korea
Correspondence
Professor Sang Hoon Ahn, Department of Internal Medicine, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, Korea. E-mail: [email protected]
Search for more papers by this authorBeom Kyung Kim
Deparment of Internal medicine, Yonsei University College of Medicine, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Liver Cirrhosis Clinical Research Center, Seoul, Korea
Search for more papers by this authorSung Hoon Choi
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Liver Cirrhosis Clinical Research Center, Seoul, Korea
Search for more papers by this authorSung Hyun Ahn
Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, Konkuk University School of Medicine, Seoul, Korea
Search for more papers by this authorAe Ri Chung
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Liver Cirrhosis Clinical Research Center, Seoul, Korea
Search for more papers by this authorYong Kwang Park
Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, Konkuk University School of Medicine, Seoul, Korea
Search for more papers by this authorKwang-Hyub Han
Deparment of Internal medicine, Yonsei University College of Medicine, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Liver Cirrhosis Clinical Research Center, Seoul, Korea
Search for more papers by this authorSeungtaek Kim
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Liver Cirrhosis Clinical Research Center, Seoul, Korea
Search for more papers by this authorHyon-Suk Kim
Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorJeon Han Park
Department of Microbiology, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorKyung Sik Kim
Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorHee Seung Lee
Deparment of Internal medicine, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorYong Sang Cho
College of Global General Education, Gachon University, Seongnam-si, Korea
Search for more papers by this authorKyun-Hwan Kim
Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, Konkuk University School of Medicine, Seoul, Korea
Search for more papers by this authorCorresponding Author
Sang Hoon Ahn
Deparment of Internal medicine, Yonsei University College of Medicine, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Liver Cirrhosis Clinical Research Center, Seoul, Korea
Correspondence
Professor Sang Hoon Ahn, Department of Internal Medicine, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, Korea. E-mail: [email protected]
Search for more papers by this authorAbstract
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 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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