Multiomics interrogation into HBV (Hepatitis B virus)-host interaction reveals novel coding potential in human genome, and identifies canonical and non-canonical proteins as host restriction factors against HBV

Abstract Hepatitis B Virus (HBV) constitutes a major threat to global public health. Current understanding of HBV-host interaction is yet limited. Here, ribosome profiling, quantitative mass spectrometry and RNA-sequencing were conducted on a recently established HBV replication system, through whic...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Shilin Yuan, Guanghong Liao, Menghuan Zhang, Yuanfei Zhu, Weidi Xiao, Kun Wang, Chuanyin Li, Caiwei Jia, Na Sun, Axel Walch, Daming Gao, Ping Xu, Qiang Deng, Jian Zhang, He Wang, Ronggui Hu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/fc77a95c75fc478a9f29455679530875
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:fc77a95c75fc478a9f29455679530875
record_format	dspace
spelling	oai:doaj.org-article:fc77a95c75fc478a9f294556795308752021-11-08T11:14:42ZMultiomics interrogation into HBV (Hepatitis B virus)-host interaction reveals novel coding potential in human genome, and identifies canonical and non-canonical proteins as host restriction factors against HBV10.1038/s41421-021-00337-32056-5968https://doaj.org/article/fc77a95c75fc478a9f294556795308752021-11-01T00:00:00Zhttps://doi.org/10.1038/s41421-021-00337-3https://doaj.org/toc/2056-5968Abstract Hepatitis B Virus (HBV) constitutes a major threat to global public health. Current understanding of HBV-host interaction is yet limited. Here, ribosome profiling, quantitative mass spectrometry and RNA-sequencing were conducted on a recently established HBV replication system, through which we identified multiomic differentially expressed genes (DEGs) that HBV orchestrated to remodel host proteostasis networks. Our multiomics interrogation revealed that HBV induced significant changes in both transcription and translation of 35 canonical genes including PPP1R15A, PGAM5 and SIRT6, as well as the expression of at least 15 non-canonical open reading frames (ncORFs) including ncPON2 and ncGRWD1, thus revealing an extra coding potential of human genome. Overexpression of these five genes but not the enzymatically deficient SIRT6 mutants suppressed HBV replication while knockdown of SIRT6 had opposite effect. Furthermore, the expression of SIRT6 was down-regulated in patients, cells or animal models of HBV infection. Mechanistic study further indicated that SIRT6 directly binds to mini-chromosome and deacetylates histone H3 lysine 9 (H3K9ac) and histone H3 lysine 56 (H3K56ac), and chemical activation of endogenous SIRT6 with MDL800 suppressed HBV infection in vitro and in vivo. By generating the first multiomics landscape of host-HBV interaction, our work is thus opening a new avenue to facilitate therapeutic development against HBV infection.Shilin YuanGuanghong LiaoMenghuan ZhangYuanfei ZhuWeidi XiaoKun WangChuanyin LiCaiwei JiaNa SunAxel WalchDaming GaoPing XuQiang DengJian ZhangHe WangRonggui HuNature Publishing GrouparticleCytologyQH573-671ENCell Discovery, Vol 7, Iss 1, Pp 1-20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Shilin Yuan Guanghong Liao Menghuan Zhang Yuanfei Zhu Weidi Xiao Kun Wang Chuanyin Li Caiwei Jia Na Sun Axel Walch Daming Gao Ping Xu Qiang Deng Jian Zhang He Wang Ronggui Hu Multiomics interrogation into HBV (Hepatitis B virus)-host interaction reveals novel coding potential in human genome, and identifies canonical and non-canonical proteins as host restriction factors against HBV
description	Abstract Hepatitis B Virus (HBV) constitutes a major threat to global public health. Current understanding of HBV-host interaction is yet limited. Here, ribosome profiling, quantitative mass spectrometry and RNA-sequencing were conducted on a recently established HBV replication system, through which we identified multiomic differentially expressed genes (DEGs) that HBV orchestrated to remodel host proteostasis networks. Our multiomics interrogation revealed that HBV induced significant changes in both transcription and translation of 35 canonical genes including PPP1R15A, PGAM5 and SIRT6, as well as the expression of at least 15 non-canonical open reading frames (ncORFs) including ncPON2 and ncGRWD1, thus revealing an extra coding potential of human genome. Overexpression of these five genes but not the enzymatically deficient SIRT6 mutants suppressed HBV replication while knockdown of SIRT6 had opposite effect. Furthermore, the expression of SIRT6 was down-regulated in patients, cells or animal models of HBV infection. Mechanistic study further indicated that SIRT6 directly binds to mini-chromosome and deacetylates histone H3 lysine 9 (H3K9ac) and histone H3 lysine 56 (H3K56ac), and chemical activation of endogenous SIRT6 with MDL800 suppressed HBV infection in vitro and in vivo. By generating the first multiomics landscape of host-HBV interaction, our work is thus opening a new avenue to facilitate therapeutic development against HBV infection.
format	article
author	Shilin Yuan Guanghong Liao Menghuan Zhang Yuanfei Zhu Weidi Xiao Kun Wang Chuanyin Li Caiwei Jia Na Sun Axel Walch Daming Gao Ping Xu Qiang Deng Jian Zhang He Wang Ronggui Hu
author_facet	Shilin Yuan Guanghong Liao Menghuan Zhang Yuanfei Zhu Weidi Xiao Kun Wang Chuanyin Li Caiwei Jia Na Sun Axel Walch Daming Gao Ping Xu Qiang Deng Jian Zhang He Wang Ronggui Hu
author_sort	Shilin Yuan
title	Multiomics interrogation into HBV (Hepatitis B virus)-host interaction reveals novel coding potential in human genome, and identifies canonical and non-canonical proteins as host restriction factors against HBV
title_short	Multiomics interrogation into HBV (Hepatitis B virus)-host interaction reveals novel coding potential in human genome, and identifies canonical and non-canonical proteins as host restriction factors against HBV
title_full	Multiomics interrogation into HBV (Hepatitis B virus)-host interaction reveals novel coding potential in human genome, and identifies canonical and non-canonical proteins as host restriction factors against HBV
title_fullStr	Multiomics interrogation into HBV (Hepatitis B virus)-host interaction reveals novel coding potential in human genome, and identifies canonical and non-canonical proteins as host restriction factors against HBV
title_full_unstemmed	Multiomics interrogation into HBV (Hepatitis B virus)-host interaction reveals novel coding potential in human genome, and identifies canonical and non-canonical proteins as host restriction factors against HBV
title_sort	multiomics interrogation into hbv (hepatitis b virus)-host interaction reveals novel coding potential in human genome, and identifies canonical and non-canonical proteins as host restriction factors against hbv
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/fc77a95c75fc478a9f29455679530875
work_keys_str_mv	AT shilinyuan multiomicsinterrogationintohbvhepatitisbvirushostinteractionrevealsnovelcodingpotentialinhumangenomeandidentifiescanonicalandnoncanonicalproteinsashostrestrictionfactorsagainsthbv AT guanghongliao multiomicsinterrogationintohbvhepatitisbvirushostinteractionrevealsnovelcodingpotentialinhumangenomeandidentifiescanonicalandnoncanonicalproteinsashostrestrictionfactorsagainsthbv AT menghuanzhang multiomicsinterrogationintohbvhepatitisbvirushostinteractionrevealsnovelcodingpotentialinhumangenomeandidentifiescanonicalandnoncanonicalproteinsashostrestrictionfactorsagainsthbv AT yuanfeizhu multiomicsinterrogationintohbvhepatitisbvirushostinteractionrevealsnovelcodingpotentialinhumangenomeandidentifiescanonicalandnoncanonicalproteinsashostrestrictionfactorsagainsthbv AT weidixiao multiomicsinterrogationintohbvhepatitisbvirushostinteractionrevealsnovelcodingpotentialinhumangenomeandidentifiescanonicalandnoncanonicalproteinsashostrestrictionfactorsagainsthbv AT kunwang multiomicsinterrogationintohbvhepatitisbvirushostinteractionrevealsnovelcodingpotentialinhumangenomeandidentifiescanonicalandnoncanonicalproteinsashostrestrictionfactorsagainsthbv AT chuanyinli multiomicsinterrogationintohbvhepatitisbvirushostinteractionrevealsnovelcodingpotentialinhumangenomeandidentifiescanonicalandnoncanonicalproteinsashostrestrictionfactorsagainsthbv AT caiweijia multiomicsinterrogationintohbvhepatitisbvirushostinteractionrevealsnovelcodingpotentialinhumangenomeandidentifiescanonicalandnoncanonicalproteinsashostrestrictionfactorsagainsthbv AT nasun multiomicsinterrogationintohbvhepatitisbvirushostinteractionrevealsnovelcodingpotentialinhumangenomeandidentifiescanonicalandnoncanonicalproteinsashostrestrictionfactorsagainsthbv AT axelwalch multiomicsinterrogationintohbvhepatitisbvirushostinteractionrevealsnovelcodingpotentialinhumangenomeandidentifiescanonicalandnoncanonicalproteinsashostrestrictionfactorsagainsthbv AT daminggao multiomicsinterrogationintohbvhepatitisbvirushostinteractionrevealsnovelcodingpotentialinhumangenomeandidentifiescanonicalandnoncanonicalproteinsashostrestrictionfactorsagainsthbv AT pingxu multiomicsinterrogationintohbvhepatitisbvirushostinteractionrevealsnovelcodingpotentialinhumangenomeandidentifiescanonicalandnoncanonicalproteinsashostrestrictionfactorsagainsthbv AT qiangdeng multiomicsinterrogationintohbvhepatitisbvirushostinteractionrevealsnovelcodingpotentialinhumangenomeandidentifiescanonicalandnoncanonicalproteinsashostrestrictionfactorsagainsthbv AT jianzhang multiomicsinterrogationintohbvhepatitisbvirushostinteractionrevealsnovelcodingpotentialinhumangenomeandidentifiescanonicalandnoncanonicalproteinsashostrestrictionfactorsagainsthbv AT hewang multiomicsinterrogationintohbvhepatitisbvirushostinteractionrevealsnovelcodingpotentialinhumangenomeandidentifiescanonicalandnoncanonicalproteinsashostrestrictionfactorsagainsthbv AT rongguihu multiomicsinterrogationintohbvhepatitisbvirushostinteractionrevealsnovelcodingpotentialinhumangenomeandidentifiescanonicalandnoncanonicalproteinsashostrestrictionfactorsagainsthbv
_version_	1718442394177765376

Multiomics interrogation into HBV (Hepatitis B virus)-host interaction reveals novel coding potential in human genome, and identifies canonical and non-canonical proteins as host restriction factors against HBV

Ejemplares similares