Yuan, S.* ; Liao, G.* ; Zhang, M.* ; Zhu, Y.* ; Xiao, W.* ; Wang, K.* ; Li, C.* ; Jia, C.* ; Sun, N. ; Walch, A.K. ; Gao, D.* ; Xu, P.* ; Deng, Q.* ; Zhang, J.* ; Wang, H.* ; Hu, R.*
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.
Cell Discov. 7:105 (2021)
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.
Impact Factor
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Times Cited
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Altmetric
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Hepatitis-b-virus; Closed Circular Dna; Histone Deacetylase Sirt6; X Protein; In-vivo; Epigenetic Regulation; Viral Persistence; Cell-culture; Amino-acids; Translation
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2021
Prepublished im Jahr
HGF-Berichtsjahr
2021
ISSN (print) / ISBN
2056-5968
e-ISSN
2056-5968
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 7,
Heft: 1,
Seiten: ,
Artikelnummer: 105
Supplement: ,
Reihe
Verlag
Springer
Verlagsort
Campus, 4 Crinan St, London, N1 9xw, England
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30205 - Bioengineering and Digital Health
Forschungsfeld(er)
Enabling and Novel Technologies
PSP-Element(e)
G-500390-001
Förderungen
Youth Innovation Promotion Association of the Chinese Academy of Sciences
National Key R&D Program of China
Shanghai Municipal Science and Technology Major Project
Strategic Priority Research Program of the Chinese Academy of Sciences
National Science and Technology Major Project
Department of Science and Technology of Zhejiang Province
Shenzhen Hong Kong Institute of Brain Science
China Postdoctoral Science Foundation
National Natural Science Foundation of China
Copyright
Erfassungsdatum
2021-12-16