Hepatitis B virus spliced variants are associated with an impaired response to interferon therapy

During hepatitis B virus (HBV) replication, spliced HBV genomes and splice-generated proteins have been widely described, however, their biological and clinical significance remains to be defined. Here, an elevation of the proportion of HBV spliced variants in the sera of patients with chronic hepat...

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Main Authors:	Chen, Jieliang, Wu, Min, Wang, Fan, Zhang, Wen, Wang, Wei, Zhang, Xiaonan, Zhang, Jiming, Liu, Yinghui, Liu, Yi, Feng, Yanling, Zheng, Ye, Hu, Yunwen, Yuan, Zhenghong
Format:	Online
Language:	English
Published:	Nature Publishing Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653653/

id	pubmed-4653653
recordtype	oai_dc
spelling	pubmed-46536532015-11-25 Hepatitis B virus spliced variants are associated with an impaired response to interferon therapy Chen, Jieliang Wu, Min Wang, Fan Zhang, Wen Wang, Wei Zhang, Xiaonan Zhang, Jiming Liu, Yinghui Liu, Yi Feng, Yanling Zheng, Ye Hu, Yunwen Yuan, Zhenghong Article During hepatitis B virus (HBV) replication, spliced HBV genomes and splice-generated proteins have been widely described, however, their biological and clinical significance remains to be defined. Here, an elevation of the proportion of HBV spliced variants in the sera of patients with chronic hepatitis B (CHB) is shown to correlate with an impaired respond to interferon-α (IFN-α) therapy. Transfection of the constructs encoding the three most dominant species of spliced variants into cells or ectopic expression of the two major spliced protein including HBSP and N-terminal-truncated viral polymerase protein result in strong suppression of IFN-α signaling transduction, while mutation of the major splicing-related sites of HBV attenuates the viral anti-IFN activities in both cell and mouse models. These results have associated the productions of HBV spliced variants with the failure response to IFN therapy and illuminate a novel mechanism where spliced viral products are employed to resist IFN-mediated host defense. Nature Publishing Group 2015-11-20 /pmc/articles/PMC4653653/ /pubmed/26585041 http://dx.doi.org/10.1038/srep16459 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Chen, Jieliang Wu, Min Wang, Fan Zhang, Wen Wang, Wei Zhang, Xiaonan Zhang, Jiming Liu, Yinghui Liu, Yi Feng, Yanling Zheng, Ye Hu, Yunwen Yuan, Zhenghong
spellingShingle	Chen, Jieliang Wu, Min Wang, Fan Zhang, Wen Wang, Wei Zhang, Xiaonan Zhang, Jiming Liu, Yinghui Liu, Yi Feng, Yanling Zheng, Ye Hu, Yunwen Yuan, Zhenghong Hepatitis B virus spliced variants are associated with an impaired response to interferon therapy
author_facet	Chen, Jieliang Wu, Min Wang, Fan Zhang, Wen Wang, Wei Zhang, Xiaonan Zhang, Jiming Liu, Yinghui Liu, Yi Feng, Yanling Zheng, Ye Hu, Yunwen Yuan, Zhenghong
author_sort	Chen, Jieliang
title	Hepatitis B virus spliced variants are associated with an impaired response to interferon therapy
title_short	Hepatitis B virus spliced variants are associated with an impaired response to interferon therapy
title_full	Hepatitis B virus spliced variants are associated with an impaired response to interferon therapy
title_fullStr	Hepatitis B virus spliced variants are associated with an impaired response to interferon therapy
title_full_unstemmed	Hepatitis B virus spliced variants are associated with an impaired response to interferon therapy
title_sort	hepatitis b virus spliced variants are associated with an impaired response to interferon therapy
description	During hepatitis B virus (HBV) replication, spliced HBV genomes and splice-generated proteins have been widely described, however, their biological and clinical significance remains to be defined. Here, an elevation of the proportion of HBV spliced variants in the sera of patients with chronic hepatitis B (CHB) is shown to correlate with an impaired respond to interferon-α (IFN-α) therapy. Transfection of the constructs encoding the three most dominant species of spliced variants into cells or ectopic expression of the two major spliced protein including HBSP and N-terminal-truncated viral polymerase protein result in strong suppression of IFN-α signaling transduction, while mutation of the major splicing-related sites of HBV attenuates the viral anti-IFN activities in both cell and mouse models. These results have associated the productions of HBV spliced variants with the failure response to IFN therapy and illuminate a novel mechanism where spliced viral products are employed to resist IFN-mediated host defense.
publisher	Nature Publishing Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653653/
_version_	1613504217082757120

Hepatitis B virus spliced variants are associated with an impaired response to interferon therapy

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