Entry
Name
Hepatitis B
Description
Hepatitis B virus (HBV) is an enveloped virus and contains a partially double-stranded relaxed circular DNA (RC-DNA) genome. After entry into hepatocytes, HBV RC-DNA is transported to the nucleus and converted into a covalently closed circular molecule cccDNA. The cccDNA is the template for transcription of all viral RNAs including the pregenomic RNA (pgRNA), encoding for 7 viral proteins: large, middle, and small envelope proteins (LHBs, MHBs, and SHBs) that form the surface antigen (HBsAg), the core antigen (HBcAg), the e antigen (HBeAg), the HBV polymerase, and the regulatory protein X (HBx). The pgRNA interacts with the viral polymerase protein to initiate the encapsidation into the core particles. Through endoplasmic reticulum, the core particles finish assembling with the envelope proteins and are released. HBV infection leads to a wide spectrum of liver diseases raging from chronic hepatitis, cirrhosis to hepatocellular carcinoma. The mechanism of liver injury is still not clear. However, HBV proteins target host proteins, involved in a variety of functions, thus regulating transcription, cellular signaling cascades, proliferation, differentiation, and apoptosis.
Class
Human Diseases; Infectious disease: viral
BRITE hierarchy
Pathway map
Ortholog table
Disease
Drug
D00353 Lamivudine (JAN/USP/INN)
D01655 Adefovir dipivoxil (USAN)
D01982 Tenofovir disoproxil fumarate (JAN/USAN)
D05588 Pradefovir mesylate (USAN)
D06278 Valtorcitabine dihydrochloride (USAN)
D10428 Tenofovir alafenamide (USAN/INN)
D10605 Tenofovir alafenamide fumarate (JAN/USAN)
D10834 Tenofovir disoproxil phosphate
D11391 Tenofovir disoproxil maleate
D12126 Bersacapavir (USAN/INN)
D12503 Linvencorvir (USAN/INN)
Orthology
K23128 Orthohepadnavirus large envelope protein
K06255 basement membrane-specific heparan sulfate proteoglycan core protein
K14341 solute carrier family 10 (sodium/bile acid cotransporter), member 1
K21854 Orthohepadnavirus protein X
K23129 Orthohepadnavirus capsid protein
K13375 transforming growth factor beta-1
K13376 transforming growth factor beta-2
K13377 transforming growth factor beta-3
K23605 mothers against decapentaplegic homolog 3
K06625 cyclin-dependent kinase inhibitor 1A
K04440 mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04377 Myc proto-oncogene protein
K12496 early growth response protein 2
K12497 early growth response protein 3
K04389 tumor necrosis factor ligand superfamily member 6
K10610 DNA damage-binding protein 1
K10140 DNA damage-binding protein 2
K16197 14-3-3 protein beta/theta/zeta
K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K02649 phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04467 inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10 ]
K07209 inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K07210 inhibitor of nuclear factor kappa-B kinase subunit gamma
K04734 NF-kappa-B inhibitor alpha
K02580 nuclear factor NF-kappa-B p105 subunit
K04735 transcription factor p65
K02161 apoptosis regulator Bcl-2
K02158 Bcl-2-antagonist of cell death
K04390 tumor necrosis factor receptor superfamily member 6
K02373 FAS-associated death domain protein
K04726 BH3 interacting domain death agonist
K02159 apoptosis regulator BAX
K02084 apoptotic protease-activating factor
K04741 caspase 12 [EC:3.4.22.-]
K08731 baculoviral IAP repeat-containing protein 5
K06626 G1/S-specific cyclin-E1
K06618 retinoblastoma-associated protein
K17454 transcription factor E2F1
K09389 transcription factor E2F2
K06620 transcription factor E2F3
K03662 V-type H+-transporting ATPase S1 subunit
K04446 nuclear factor of activated T-cells, cytoplasmic 1
K17332 nuclear factor of activated T-cells, cytoplasmic 2
K17333 nuclear factor of activated T-cells, cytoplasmic 3
K17334 nuclear factor of activated T-cells, cytoplasmic 4
K03156 tumor necrosis factor superfamily, member 2
K04692 signal transducer and activator of transcription 3
K11220 signal transducer and activator of transcription 1
K11221 signal transducer and activator of transcription 2
K11222 signal transducer and activator of transcription 4
K11223 signal transducer and activator of transcription 5A
K11224 signal transducer and activator of transcription 5B
K11225 signal transducer and activator of transcription 6
K15041 voltage-dependent anion channel protein 3
K04364 growth factor receptor-bound protein 2
K04448 transcription factor AP-1
K04501 mothers against decapentaplegic homolog 4
K04450 cyclic AMP-dependent transcription factor ATF-2
K05870 cyclic AMP-responsive element-binding protein 1
K09048 cyclic AMP-responsive element-binding protein 3
K04374 cyclic AMP-dependent transcription factor ATF-4
K09047 cyclic AMP-responsive element-binding protein 5
K09049 cyclic AMP-dependent transcription factor ATF-6 beta
K04802 proliferating cell nuclear antigen
K08845 A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04365 B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04379 proto-oncogene protein c-fos
K04375 ETS domain-containing protein Elk-1
K04729 myeloid differentiation primary response protein MyD88
K05403 toll-interleukin 1 receptor (TIR) domain-containing adaptor protein
K05409 TRIF-related adaptor molecule
K05842 toll-like receptor adapter molecule 1
K12647 interferon-induced helicase C domain-containing protein 1 [EC:3.6.4.13 ]
K12648 mitochondrial antiviral-signaling protein
K03174 TNF receptor-associated factor 3
K07211 inhibitor of nuclear factor kappa-B kinase subunit epsilon [EC:2.7.11.10 ]
K05411 interferon regulatory factor 3
K09447 interferon regulatory factor 7
Compound
Reference
Authors
Caballero A, Tabernero D, Buti M, Rodriguez-Frias F
Title
Hepatitis B virus: The challenge of an ancient virus with multiple faces and a remarkable replication strategy.
Journal
Reference
Authors
Walsh R, Locarnini S
Title
Hepatitis B precore protein: pathogenic potential and therapeutic promise.
Journal
Reference
Authors
Liang TJ, Block TM, McMahon BJ, Ghany MG, Urban S, Guo JT, Locarnini S, Zoulim F, Chang KM, Lok AS
Title
Present and future therapies of hepatitis B: From discovery to cure.
Journal
Reference
Authors
Morikawa K, Suda G, Sakamoto N
Title
Viral life cycle of hepatitis B virus: Host factors and druggable targets.
Journal
Reference
Authors
Feitelson MA, Reis HM, Tufan NL, Sun B, Pan J, Lian Z
Title
Putative roles of hepatitis B x antigen in the pathogenesis of chronic liver disease.
Journal
Reference
Authors
Murata M, Matsuzaki K, Yoshida K, Sekimoto G, Tahashi Y, Mori S, Uemura Y, Sakaida N, Fujisawa J, Seki T, Kobayashi K, Yokote K, Koike K, Okazaki K
Title
Hepatitis B virus X protein shifts human hepatic transforming growth factor (TGF)-beta signaling from tumor suppression to oncogenesis in early chronic hepatitis B.
Journal
Reference
Authors
Yoo YG, Lee MO
Title
Hepatitis B virus X protein induces expression of Fas ligand gene through enhancing transcriptional activity of early growth response factor.
Journal
Reference
Authors
Zhang X, Zhang H, Ye L
Title
Effects of hepatitis B virus X protein on the development of liver cancer.
Journal
Reference
Authors
Benhenda S, Cougot D, Buendia MA, Neuveut C
Title
Hepatitis B virus X protein molecular functions and its role in virus life cycle and pathogenesis.
Journal
Reference
Authors
Benhenda S, Cougot D, Neuveut C, Buendia MA
Title
Liver cell transformation in chronic HBV infection.
Journal
Reference
Authors
Diao J, Khine AA, Sarangi F, Hsu E, Iorio C, Tibbles LA, Woodgett JR, Penninger J, Richardson CD
Title
X protein of hepatitis B virus inhibits Fas-mediated apoptosis and is associated with up-regulation of the SAPK/JNK pathway.
Journal
Reference
Authors
Park NH, Song IH, Chung YH
Title
Chronic hepatitis B in hepatocarcinogenesis.
Journal
Reference
Authors
Lin S, Zhang YJ
Title
Interference of Apoptosis by Hepatitis B Virus.
Journal
Reference
Authors
Zhang X, Dong N, Yin L, Cai N, Ma H, You J, Zhang H, Wang H, He R, Ye L
Title
Hepatitis B virus X protein upregulates survivin expression in hepatoma tissues.
Journal
Reference
Authors
Kim HJ, Kim SY, Kim J, Lee H, Choi M, Kim JK, Ahn JK
Title
Hepatitis B virus X protein induces apoptosis by enhancing translocation of Bax to mitochondria.
Journal
Reference
Authors
Ng SA, Lee C
Title
Hepatitis B virus X gene and hepatocarcinogenesis.
Journal
Reference
Authors
Cong YS, Yao YL, Yang WM, Kuzhandaivelu N, Seto E
Title
The hepatitis B virus X-associated protein, XAP3, is a protein kinase C-binding protein.
Journal
Reference
Authors
Panteva M, Korkaya H, Jameel S
Title
Hepatitis viruses and the MAPK pathway: is this a survival strategy?
Journal
Reference
Authors
Lee YH, Yun Y
Title
HBx protein of hepatitis B virus activates Jak1-STAT signaling.
Journal
Reference
Authors
Tan A, Yeh SH, Liu CJ, Cheung C, Chen PJ
Title
Viral hepatocarcinogenesis: from infection to cancer.
Journal
Reference
Authors
Chami M, Oules B, Paterlini-Brechot P
Title
Cytobiological consequences of calcium-signaling alterations induced by human viral proteins.
Journal
Reference
Authors
Ganem D
Title
Virology. The X files--one step closer to closure.
Journal
Reference
Authors
Chung TW, Lee YC, Kim CH
Title
Hepatitis B viral HBx induces matrix metalloproteinase-9 gene expression through activation of ERK and PI-3K/AKT pathways: involvement of invasive potential.
Journal
Reference
Authors
Gurtsevitch VE
Title
Human oncogenic viruses: hepatitis B and hepatitis C viruses and their role in hepatocarcinogenesis.
Journal
Reference
Authors
Schadler S, Hildt E
Title
HBV life cycle: entry and morphogenesis.
Journal
Reference
Authors
Ortega-Prieto AM, Dorner M
Title
Immune Evasion Strategies during Chronic Hepatitis B and C Virus Infection.
Journal
Reference
Authors
Nosratabadi R, Alavian SM, Zare-Bidaki M, Shahrokhi VM, Arababadi MK
Title
Innate immunity related pathogen recognition receptors and chronic hepatitis B infection.
Journal
Reference
Authors
Bagheri V, Askari A, Arababadi MK, Kennedy D
Title
Can Toll-Like Receptor (TLR) 2 be considered as a new target for immunotherapy against hepatitis B infection?
Journal
Reference
Authors
Zhang E, Lu M
Title
Toll-like receptor (TLR)-mediated innate immune responses in the control of hepatitis B virus (HBV) infection.
Journal
Reference
Authors
Yu S, Chen J, Wu M, Chen H, Kato N, Yuan Z
Title
Hepatitis B virus polymerase inhibits RIG-I- and Toll-like receptor 3-mediated beta interferon induction in human hepatocytes through interference with interferon regulatory factor 3 activation and dampening of the interaction between TBK1/IKKepsilon and DDX3.
Journal
Reference
Authors
Revill P, Yuan Z
Title
New insights into how HBV manipulates the innate immune response to establish acute and persistent infection.
Journal
Reference
Authors
Hopcraft SE, Damania B
Title
Tumour viruses and innate immunity.
Journal
Reference
Authors
Dandri M, Locarnini S
Title
New insight in the pathobiology of hepatitis B virus infection.
Journal
Related pathway
ko04064 NF-kappa B signaling pathway
ko04620 Toll-like receptor signaling pathway
ko04622 RIG-I-like receptor signaling pathway
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