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.
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.
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对 HBV（乙型肝炎病毒）-宿主相互作用的多组学研究揭示了人类基因组中新的编码潜力，并确定了经典和非经典蛋白质作为针对 HBV 的宿主限制因素
DOI：
10.1038/s41421-021-00337-3
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发表时间：
2021-11-02
期刊：
影响因子：
33.5
通讯作者：
Hu R
中科院分区：
文献类型：
--
作者：
Yuan S;Liao G;Zhang M;Zhu Y;Xiao W;Wang K;Li C;Jia C;Sun N;Walch A;Gao D;Xu P;Deng Q;Zhang J;Wang H;Hu R
B型肝炎病毒（HBV）是全球公共卫生的主要威胁。目前对HBV-宿主相互作用的理解仍然有限。在这里，核糖体分析，定量质谱和RNA测序进行了最近建立的HBV复制系统，通过该系统，我们确定了多组差异表达基因（DEG），HBV精心策划重塑主机蛋白质稳定网络。我们的多组学研究发现，HBV诱导了包括PPP 1 R15 A、PGAM 5和SIRT 6在内的35个经典基因的转录和翻译，以及包括ncPON 2和ncGRWD 1在内的至少15个非经典开放阅读框架（ncORF）的表达，从而揭示了人类基因组的额外编码潜力。这五个基因的过表达抑制了HBV复制，而SIRT 6酶缺陷突变体则没有抑制作用，而SIRT 6的敲低则具有相反的作用。此外，SIRT 6的表达在HBV感染的患者、细胞或动物模型中下调。机制研究进一步表明，SIRT 6直接结合到微型染色体上并使组蛋白H3赖氨酸9（H3 K9 ac）和组蛋白H3赖氨酸56（H3 K56 ac）脱乙酰化，并且用MDL 800化学活化内源性SIRT 6在体外和体内抑制HBV感染。通过产生宿主-HBV相互作用的第一个多组学景观，我们的工作因此开辟了一条新的途径，以促进针对HBV感染的治疗开发。
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.
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影响因子：
6.7
作者：
Lamontagne J;Mell JC;Bouchard MJ
通讯作者：
Bouchard MJ
影响因子：
13.8
作者：
Kugel, Site;Mostoslavsky, Raul
通讯作者：
Mostoslavsky, Raul
编程的核糖体框架从同一基因产生铜转运蛋白和铜伴侣。
影响因子：
16
作者：
Meydan S;Klepacki D;Karthikeyan S;Margus T;Thomas P;Jones JE;Khan Y;Briggs J;Dinman JD;Vázquez-Laslop N;Mankin AS
通讯作者：
Mankin AS
基于RNA-SEQ的转录组分析乙型肝炎病毒（HEV）和丙型肝炎病毒（HBV）复制子转染了HUH-7细胞。
影响因子：
3.7
作者：
Jagya N;Varma SP;Thakral D;Joshi P;Durgapal H;Panda SK
通讯作者：
Panda SK
影响因子：
21.3
作者：
Etchegaray JP;Chavez L;Huang Y;Ross KN;Choi J;Martinez-Pastor B;Walsh RM;Sommer CA;Lienhard M;Gladden A;Kugel S;Silberman DM;Ramaswamy S;Mostoslavsky G;Hochedlinger K;Goren A;Rao A;Mostoslavsky R
通讯作者：
Mostoslavsky R