Entry
Name
Hepatitis B - Homo sapiens (human)
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
Network
Element
N00267 HBV HBx to PI3K signaling pathway
N00268 HBV HBx to RIG-I-like receptor signaling pathway
N00531 HBV HBx to TGF-beta signaling pathway
N00532 HBV HBx to Egr-mediated transcription
N00533 HBV HBx to Crosstalk between extrinsic and intrinsic apoptotic pathways
N00534 HBV HBx to Crosstalk between extrinsic and intrinsic apoptotic pathways
N00535 HBV HBx to p53-mediated transcription
N00537 HBV HBx to cell cycle G1/S
N00539 HBV HBx to Ca2+-PYK2-RAS-ERK signaling pathway
N00540 HBV HBx to RAS-ERK signaling pathway
N00541 HBV HBx to RAS-ERK signaling pathway
N00543 HBV HBx to JNK signaling pathway
N00544 HBV HBx to CREB-mediated transcription
N00545 HBV HBx to ERK signaling pathway
N00547 HBV LHBs to PKC-ERK signaling pathway
N00548 HBV HBx to Jak-STAT signaling pathway
N00549 HBV HBeAg to TLR2/4-NFKB signaling pathway
N00550 HBV HBeAg to TLR2/4-NFKB signaling pathway
N00551 HBV HBs to TLR2/4-MAPK signaling pathway
N00552 HBV pol to TLR3-IRF3 signaling pathway
N00554 HBV HBe to TLR4-IRF3/7 signaling pathway
N00555 HBV HBe to TLR4-IRF3/7 signaling pathway
N00556 HBV HBe to TLR2/4-NFKB signaling pathway
N00557 HBV HBe to TLR2/4-NFKB signaling pathway
N00558 HBV pol to IFN signaling pathway
Disease
Drug
D02745 Interferon alfa-2b (USAN)
D02747 Peginterferon alfa-2a (USAN/INN)
D03305 Interferon alfa (NAMALWA) (JP18)
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
3339 HSPG2; heparan sulfate proteoglycan 2 [KO:K06255 ]
6554 SLC10A1; solute carrier family 10 member 1 [KO:K14341 ]
7040 TGFB1; transforming growth factor beta 1 [KO:K13375 ]
7042 TGFB2; transforming growth factor beta 2 [KO:K13376 ]
7043 TGFB3; transforming growth factor beta 3 [KO:K13377 ]
1026 CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625 ]
4609 MYC; MYC proto-oncogene, bHLH transcription factor [KO:K04377 ]
1642 DDB1; damage specific DNA binding protein 1 [KO:K10610 ]
1643 DDB2; damage specific DNA binding protein 2 [KO:K10140 ]
7534 YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197 ]
7529 YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197 ]
10971 YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197 ]
5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
5295 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
5296 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
8503 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
1147 CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467 ] [EC:2.7.11.10 ]
8517 IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210 ]
4790 NFKB1; nuclear factor kappa B subunit 1 [KO:K02580 ]
5970 RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735 ]
596 BCL2; BCL2 apoptosis regulator [KO:K02161 ]
572 BAD; BCL2 associated agonist of cell death [KO:K02158 ]
355 FAS; Fas cell surface death receptor [KO:K04390 ]
8772 FADD; Fas associated via death domain [KO:K02373 ]
637 BID; BH3 interacting domain death agonist [KO:K04726 ]
581 BAX; BCL2 associated X, apoptosis regulator [KO:K02159 ]
317 APAF1; apoptotic peptidase activating factor 1 [KO:K02084 ]
332 BIRC5; baculoviral IAP repeat containing 5 [KO:K08731 ]
5925 RB1; RB transcriptional corepressor 1 [KO:K06618 ]
537 ATP6AP1; ATPase H+ transporting accessory protein 1 [KO:K03662 ]
4772 NFATC1; nuclear factor of activated T cells 1 [KO:K04446 ]
4773 NFATC2; nuclear factor of activated T cells 2 [KO:K17332 ]
4775 NFATC3; nuclear factor of activated T cells 3 [KO:K17333 ]
4776 NFATC4; nuclear factor of activated T cells 4 [KO:K17334 ]
6774 STAT3; signal transducer and activator of transcription 3 [KO:K04692 ]
6772 STAT1; signal transducer and activator of transcription 1 [KO:K11220 ]
6773 STAT2; signal transducer and activator of transcription 2 [KO:K11221 ]
6775 STAT4; signal transducer and activator of transcription 4 [KO:K11222 ]
6776 STAT5A; signal transducer and activator of transcription 5A [KO:K11223 ]
6777 STAT5B; signal transducer and activator of transcription 5B [KO:K11224 ]
6778 STAT6; signal transducer and activator of transcription 6 [KO:K11225 ]
7419 VDAC3; voltage dependent anion channel 3 [KO:K15041 ]
2885 GRB2; growth factor receptor bound protein 2 [KO:K04364 ]
6654 SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
6655 SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
3265 HRAS; HRas proto-oncogene, GTPase [KO:K02833 ]
3845 KRAS; KRAS proto-oncogene, GTPase [KO:K07827 ]
4893 NRAS; NRAS proto-oncogene, GTPase [KO:K07828 ]
3725 JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448 ]
1386 ATF2; activating transcription factor 2 [KO:K04450 ]
1385 CREB1; cAMP responsive element binding protein 1 [KO:K05870 ]
10488 CREB3; cAMP responsive element binding protein 3 [KO:K09048 ]
90993 CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048 ]
64764 CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048 ]
84699 CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048 ]
148327 CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048 ]
468 ATF4; activating transcription factor 4 [KO:K04374 ]
9586 CREB5; cAMP responsive element binding protein 5 [KO:K09047 ]
1388 ATF6B; activating transcription factor 6 beta [KO:K09049 ]
3576 CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030 ]
5111 PCNA; proliferating cell nuclear antigen [KO:K04802 ]
2353 FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379 ]
2002 ELK1; ETS transcription factor ELK1 [KO:K04375 ]
4615 MYD88; MYD88 innate immune signal transduction adaptor [KO:K04729 ]
114609 TIRAP; TIR domain containing adaptor protein [KO:K05403 ]
10454 TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403 ]
23118 TAB2; TGF-beta activated kinase 1 (MAP3K7) binding protein 2 [KO:K04404 ]
353376 TICAM2; TIR domain containing adaptor molecule 2 [KO:K05409 ]
148022 TICAM1; TIR domain containing adaptor molecule 1 [KO:K05842 ]
57506 MAVS; mitochondrial antiviral signaling protein [KO:K12648 ]
7187 TRAF3; TNF receptor associated factor 3 [KO:K03174 ]
9641 IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211 ] [EC:2.7.11.10 ]
3661 IRF3; interferon regulatory factor 3 [KO:K05411 ]
3665 IRF7; interferon regulatory factor 7 [KO:K09447 ]
3454 IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130 ]
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
hsa04620 Toll-like receptor signaling pathway
hsa04622 RIG-I-like receptor signaling pathway
KO pathway