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: viralBRITE hierarchy
Pathway map 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 K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K02084 APAF1; apoptotic protease-activating factor
K02158 BAD; Bcl-2-antagonist of cell death
K02159 BAX; apoptosis regulator BAX
K02161 BCL2; apoptosis regulator Bcl-2
K02373 FADD; FAS-associated death domain protein
K02580 NFKB1; nuclear factor NF-kappa-B p105 subunit
K02649 PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K03156 TNF, TNFA; tumor necrosis factor superfamily, member 2
K03174 TRAF3; TNF receptor-associated factor 3
K03662 ATPeVS1, ATP6S1; V-type H+-transporting ATPase S1 subunit
K04364 GRB2; growth factor receptor-bound protein 2
K04365 BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04366 RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04368 MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2 ]
K04369 MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2 ]
K04374 ATF4, CREB2; cyclic AMP-dependent transcription factor ATF-4
K04375 ELK1; ETS domain-containing protein Elk-1
K04377 MYC; Myc proto-oncogene protein
K04379 FOS; proto-oncogene protein c-fos
K04389 TNFSF6, FASL, CD178; tumor necrosis factor ligand superfamily member 6
K04390 TNFRSF6, FAS, CD95; tumor necrosis factor receptor superfamily member 6
K04403 MAP3K7IP1, TAB1; TAK1-binding protein 1
K04404 MAP3K7IP2, TAB2; TAK1-binding protein 2
K04416 MAP3K1, MEKK1; mitogen-activated protein kinase kinase kinase 1 [EC:2.7.11.25 ]
K04427 MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25 ]
K04430 MAP2K4, MKK4; mitogen-activated protein kinase kinase 4 [EC:2.7.12.2 ]
K04431 MAP2K7, MKK7; mitogen-activated protein kinase kinase 7 [EC:2.7.12.2 ]
K04432 MAP2K3, MKK3; mitogen-activated protein kinase kinase 3 [EC:2.7.12.2 ]
K04433 MAP2K6, MKK6; mitogen-activated protein kinase kinase 6 [EC:2.7.12.2 ]
K04440 JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04446 NFATC1, NFAT2, NFATC; nuclear factor of activated T-cells, cytoplasmic 1
K04448 JUN; transcription factor AP-1
K04450 ATF2, CREBP1; cyclic AMP-dependent transcription factor ATF-2
K04451 TP53, P53; tumor protein p53
K04467 IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10 ]
K04501 SMAD4; mothers against decapentaplegic homolog 4
K04692 STAT3; signal transducer and activator of transcription 3
K04726 BID; BH3 interacting domain death agonist
K04729 MYD88; myeloid differentiation primary response protein MyD88
K04730 IRAK1; interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1 ]
K04733 IRAK4; interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1 ]
K04734 NFKBIA; NF-kappa-B inhibitor alpha
K04735 RELA; transcription factor p65
K04741 CASP12; caspase 12 [EC:3.4.22.-]
K04802 PCNA; proliferating cell nuclear antigen
K05130 IFNAR1; interferon receptor 1
K05401 TLR3, CD283; toll-like receptor 3
K05403 TIRAP; toll-interleukin 1 receptor (TIR) domain-containing adaptor protein
K05409 TIRP, TRAM; TRIF-related adaptor molecule
K05411 IRF3; interferon regulatory factor 3
K05842 TRIF; toll-like receptor adapter molecule 1
K05870 CREB1; cyclic AMP-responsive element-binding protein 1
K06255 HSPG2; basement membrane-specific heparan sulfate proteoglycan core protein
K06618 RB1; retinoblastoma-associated protein
K06620 E2F3; transcription factor E2F3
K06625 CDKN1A, P21, CIP1; cyclin-dependent kinase inhibitor 1A
K06626 CCNE; G1/S-specific cyclin-E1
K07209 IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K07210 IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma
K07211 IKBKE, IKKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [EC:2.7.11.10 ]
K07827 KRAS, KRAS2; GTPase KRas
K08731 BIRC5; baculoviral IAP repeat-containing protein 5
K08845 ARAF, ARAF1; A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K09047 CREB5, CREBPA; cyclic AMP-responsive element-binding protein 5
K09048 CREB3; cyclic AMP-responsive element-binding protein 3
K09049 ATF6B, CREBL1; cyclic AMP-dependent transcription factor ATF-6 beta
K09389 E2F2; transcription factor E2F2
K09447 IRF7; interferon regulatory factor 7
K10030 IL8, CXCL8; interleukin 8
K10140 DDB2; DNA damage-binding protein 2
K10159 TLR2, CD282; toll-like receptor 2
K10160 TLR4, CD284; toll-like receptor 4
K10610 DDB1; DNA damage-binding protein 1
K11220 STAT1; signal transducer and activator of transcription 1
K11221 STAT2; signal transducer and activator of transcription 2
K11222 STAT4; signal transducer and activator of transcription 4
K11223 STAT5A; signal transducer and activator of transcription 5A
K11224 STAT5B; signal transducer and activator of transcription 5B
K11225 STAT6; signal transducer and activator of transcription 6
K12496 EGR2; early growth response protein 2
K12497 EGR3; early growth response protein 3
K12646 RIGI, DDX58; ATP-dependent RNA helicase DDX58 [EC:5.6.2.6 ]
K12647 IFIH1, MDA5; interferon-induced helicase C domain-containing protein 1 [EC:5.6.2.6 ]
K12648 MAVS, IPS1; mitochondrial antiviral-signaling protein
K13375 TGFB1; transforming growth factor beta-1
K13376 TGFB2; transforming growth factor beta-2
K13377 TGFB3; transforming growth factor beta-3
K14341 SLC10A1, NTCP; solute carrier family 10 (sodium/bile acid cotransporter), member 1
K15041 VDAC3; voltage-dependent anion channel protein 3
K16197 YWHAB_Q_Z; 14-3-3 protein beta/theta/zeta
K17332 NFATC2, NFAT1, NFATP; nuclear factor of activated T-cells, cytoplasmic 2
K17333 NFATC3, NFAT4; nuclear factor of activated T-cells, cytoplasmic 3
K17334 NFATC4, NFAT3; nuclear factor of activated T-cells, cytoplasmic 4
K17454 E2F1; transcription factor E2F1
K21854 X; Orthohepadnavirus protein X
K23128 S; Orthohepadnavirus large envelope protein
K23129 C; Orthohepadnavirus capsid protein
K23605 SMAD3; mothers against decapentaplegic homolog 3
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 ko04064 NF-kappa B signaling pathway
ko04620 Toll-like receptor signaling pathway
ko04622 RIG-I-like receptor signaling pathway
