Enhanced antiviral and antifibrotic effects of short hairpin RNAs targeting HBV and TGF-β in HBV-persistent mice

Abstract The hepatitis B virus (HBV) causes acute and chronic liver infection, which may lead to liver cirrhosis and hepatocellular carcinoma. Current treatments including interferons and nucleotide analogs, have limited therapeutic effects, underscoring the need to identify effective therapeutic op...

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Autores principales:	Lei Ye, Fangming Kan, Tao Yan, Jiaqi Cao, Leiliang Zhang, Zhijian Wu, Wuping Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e253775021ad435393e4863eb8c4f7ce
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spelling	oai:doaj.org-article:e253775021ad435393e4863eb8c4f7ce2021-12-02T16:07:01ZEnhanced antiviral and antifibrotic effects of short hairpin RNAs targeting HBV and TGF-β in HBV-persistent mice10.1038/s41598-017-04170-12045-2322https://doaj.org/article/e253775021ad435393e4863eb8c4f7ce2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04170-1https://doaj.org/toc/2045-2322Abstract The hepatitis B virus (HBV) causes acute and chronic liver infection, which may lead to liver cirrhosis and hepatocellular carcinoma. Current treatments including interferons and nucleotide analogs, have limited therapeutic effects, underscoring the need to identify effective therapeutic options to inhibit HBV replication and prevent complications. Previous animal models mimicking chronic HBV infection do not faithfully reflect disease progression in humans. Here, we used our established HBV-persistent mouse line with liver fibrosis to evaluate the efficacy of novel therapies. The combination of two short hairpin RNAs (dual-shRNA) against different coding regions of HBV delivered by a self-complementary AAV vector showed better antiviral effects than single shRNA both in vitro and in HBV-persistent mice. The dual-shRNA also exhibited stronger antifibrotic activity in vivo. Vector carrying shRNA against TGF-β, though did not inhibit HBV replication alone, enhanced the antiviral and antifibrotic activities of single and dual HBV shRNAs. Co-administration of TGF-β shRNA and HBV dual-shRNA decreased HBV DNA, HBV RNA, HBsAg, HBeAg, and liver fibrosis markers in serum and tissues, and improved liver morphology more effectively than single treatments. Our results suggest that the combination of shRNAs against HBV and TGF-β could be developed into a viable treatment for human HBV infection.Lei YeFangming KanTao YanJiaqi CaoLeiliang ZhangZhijian WuWuping LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lei Ye Fangming Kan Tao Yan Jiaqi Cao Leiliang Zhang Zhijian Wu Wuping Li Enhanced antiviral and antifibrotic effects of short hairpin RNAs targeting HBV and TGF-β in HBV-persistent mice
description	Abstract The hepatitis B virus (HBV) causes acute and chronic liver infection, which may lead to liver cirrhosis and hepatocellular carcinoma. Current treatments including interferons and nucleotide analogs, have limited therapeutic effects, underscoring the need to identify effective therapeutic options to inhibit HBV replication and prevent complications. Previous animal models mimicking chronic HBV infection do not faithfully reflect disease progression in humans. Here, we used our established HBV-persistent mouse line with liver fibrosis to evaluate the efficacy of novel therapies. The combination of two short hairpin RNAs (dual-shRNA) against different coding regions of HBV delivered by a self-complementary AAV vector showed better antiviral effects than single shRNA both in vitro and in HBV-persistent mice. The dual-shRNA also exhibited stronger antifibrotic activity in vivo. Vector carrying shRNA against TGF-β, though did not inhibit HBV replication alone, enhanced the antiviral and antifibrotic activities of single and dual HBV shRNAs. Co-administration of TGF-β shRNA and HBV dual-shRNA decreased HBV DNA, HBV RNA, HBsAg, HBeAg, and liver fibrosis markers in serum and tissues, and improved liver morphology more effectively than single treatments. Our results suggest that the combination of shRNAs against HBV and TGF-β could be developed into a viable treatment for human HBV infection.
format	article
author	Lei Ye Fangming Kan Tao Yan Jiaqi Cao Leiliang Zhang Zhijian Wu Wuping Li
author_facet	Lei Ye Fangming Kan Tao Yan Jiaqi Cao Leiliang Zhang Zhijian Wu Wuping Li
author_sort	Lei Ye
title	Enhanced antiviral and antifibrotic effects of short hairpin RNAs targeting HBV and TGF-β in HBV-persistent mice
title_short	Enhanced antiviral and antifibrotic effects of short hairpin RNAs targeting HBV and TGF-β in HBV-persistent mice
title_full	Enhanced antiviral and antifibrotic effects of short hairpin RNAs targeting HBV and TGF-β in HBV-persistent mice
title_fullStr	Enhanced antiviral and antifibrotic effects of short hairpin RNAs targeting HBV and TGF-β in HBV-persistent mice
title_full_unstemmed	Enhanced antiviral and antifibrotic effects of short hairpin RNAs targeting HBV and TGF-β in HBV-persistent mice
title_sort	enhanced antiviral and antifibrotic effects of short hairpin rnas targeting hbv and tgf-β in hbv-persistent mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e253775021ad435393e4863eb8c4f7ce
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Enhanced antiviral and antifibrotic effects of short hairpin RNAs targeting HBV and TGF-β in HBV-persistent mice

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