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Naturally Occurring Mutations within HBV Surface Promoter II Sequences Affect Transcription Activity, HBsAg and HBV DNA Levels in HBeAg-Positive Chronic Hepatitis B Patients

Mutations in hepatitis B virus (HBV) surface promoter II (SPII) have not been well studied in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. We aimed to investigate SPII mutations in such patients and their biological and clinical impacts. Direct sequencing was used to de...

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Autores principales: Hao, Ran, Xiang, Kuanhui, Shi, Yan, Zhao, Dong, Tian, Huifang, Xu, Baohong, Zhu, Yufang, Dong, Huan, Ding, Hai, Zhuang, Hui, Hu, Jie, Li, Tong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356792/
https://www.ncbi.nlm.nih.gov/pubmed/30669266
http://dx.doi.org/10.3390/v11010078
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author Hao, Ran
Xiang, Kuanhui
Shi, Yan
Zhao, Dong
Tian, Huifang
Xu, Baohong
Zhu, Yufang
Dong, Huan
Ding, Hai
Zhuang, Hui
Hu, Jie
Li, Tong
author_facet Hao, Ran
Xiang, Kuanhui
Shi, Yan
Zhao, Dong
Tian, Huifang
Xu, Baohong
Zhu, Yufang
Dong, Huan
Ding, Hai
Zhuang, Hui
Hu, Jie
Li, Tong
author_sort Hao, Ran
collection PubMed
description Mutations in hepatitis B virus (HBV) surface promoter II (SPII) have not been well studied in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. We aimed to investigate SPII mutations in such patients and their biological and clinical impacts. Direct sequencing was used to detect SPII mutations in 106 HBeAg-positive treatment-naïve CHB patients with genotype C (82.1% (87/106) was C2) HBV infection. Results showed that mutation frequency in transcription factor (TF) unbinding region was significantly higher than that in TF binding region of SPII (C1: 3.4% vs. 1.3%; C2: 2.6% vs. 1.3%; p < 0.0001). Luciferase assay revealed distinct promoter activities among SPII mutants; especially SPII of G120A mutant had a 15-fold higher activity than that of wild-type (p < 0.001). In vitro experiments in HepG2 cells showed that G82A, A115C and G120A mutants increased the hepatitis B surface antigen (HBsAg) levels, while C18T had an opposite effect. G82A, A115C and G120A mutants boosted the intracellular HBV total RNA level. G120A mutation resulted in an increased HBV DNA level in vitro, consistent with the serological results in patients. Thus, novel SPII mutations would affect promoter activity, HBsAg, HBV DNA and HBV total RNA levels, suggesting their potential biological and clinical significances.
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spelling pubmed-63567922019-02-05 Naturally Occurring Mutations within HBV Surface Promoter II Sequences Affect Transcription Activity, HBsAg and HBV DNA Levels in HBeAg-Positive Chronic Hepatitis B Patients Hao, Ran Xiang, Kuanhui Shi, Yan Zhao, Dong Tian, Huifang Xu, Baohong Zhu, Yufang Dong, Huan Ding, Hai Zhuang, Hui Hu, Jie Li, Tong Viruses Article Mutations in hepatitis B virus (HBV) surface promoter II (SPII) have not been well studied in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. We aimed to investigate SPII mutations in such patients and their biological and clinical impacts. Direct sequencing was used to detect SPII mutations in 106 HBeAg-positive treatment-naïve CHB patients with genotype C (82.1% (87/106) was C2) HBV infection. Results showed that mutation frequency in transcription factor (TF) unbinding region was significantly higher than that in TF binding region of SPII (C1: 3.4% vs. 1.3%; C2: 2.6% vs. 1.3%; p < 0.0001). Luciferase assay revealed distinct promoter activities among SPII mutants; especially SPII of G120A mutant had a 15-fold higher activity than that of wild-type (p < 0.001). In vitro experiments in HepG2 cells showed that G82A, A115C and G120A mutants increased the hepatitis B surface antigen (HBsAg) levels, while C18T had an opposite effect. G82A, A115C and G120A mutants boosted the intracellular HBV total RNA level. G120A mutation resulted in an increased HBV DNA level in vitro, consistent with the serological results in patients. Thus, novel SPII mutations would affect promoter activity, HBsAg, HBV DNA and HBV total RNA levels, suggesting their potential biological and clinical significances. MDPI 2019-01-18 /pmc/articles/PMC6356792/ /pubmed/30669266 http://dx.doi.org/10.3390/v11010078 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hao, Ran
Xiang, Kuanhui
Shi, Yan
Zhao, Dong
Tian, Huifang
Xu, Baohong
Zhu, Yufang
Dong, Huan
Ding, Hai
Zhuang, Hui
Hu, Jie
Li, Tong
Naturally Occurring Mutations within HBV Surface Promoter II Sequences Affect Transcription Activity, HBsAg and HBV DNA Levels in HBeAg-Positive Chronic Hepatitis B Patients
title Naturally Occurring Mutations within HBV Surface Promoter II Sequences Affect Transcription Activity, HBsAg and HBV DNA Levels in HBeAg-Positive Chronic Hepatitis B Patients
title_full Naturally Occurring Mutations within HBV Surface Promoter II Sequences Affect Transcription Activity, HBsAg and HBV DNA Levels in HBeAg-Positive Chronic Hepatitis B Patients
title_fullStr Naturally Occurring Mutations within HBV Surface Promoter II Sequences Affect Transcription Activity, HBsAg and HBV DNA Levels in HBeAg-Positive Chronic Hepatitis B Patients
title_full_unstemmed Naturally Occurring Mutations within HBV Surface Promoter II Sequences Affect Transcription Activity, HBsAg and HBV DNA Levels in HBeAg-Positive Chronic Hepatitis B Patients
title_short Naturally Occurring Mutations within HBV Surface Promoter II Sequences Affect Transcription Activity, HBsAg and HBV DNA Levels in HBeAg-Positive Chronic Hepatitis B Patients
title_sort naturally occurring mutations within hbv surface promoter ii sequences affect transcription activity, hbsag and hbv dna levels in hbeag-positive chronic hepatitis b patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356792/
https://www.ncbi.nlm.nih.gov/pubmed/30669266
http://dx.doi.org/10.3390/v11010078
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