# New Insights into the Role of NF-κB in Hepatitis B Virus Infection

**Authors:** Shana Halemubieke, Xinru Liu, Ying Yan, Huimin Ji, Huizhen Sun, Jie Ma, Le Chang, Lunan Wang

PMC · DOI: 10.7150/ijbs.126968 · 2026-02-11

## TL;DR

This paper explores how the NF-κB pathway interacts with hepatitis B virus proteins and affects liver disease.

## Contribution

The paper provides a summary of HBV proteins' interactions with the NF-κB pathway and their implications for liver disease.

## Key findings

- HBV proteins interact with NF-κB pathway components to modulate immune responses.
- Activation or suppression of NF-κB by HBV may contribute to liver disease progression.
- Understanding these interactions could reveal new therapeutic targets for HBV.

## Abstract

The nuclear factor kappaB (NF-κB) is a critical regulator in immune development, responses, and tumorigenesis. A range of signals can stimulate its activation by interacting with the inhibitor of κB (IκB) and IκB kinase (IKK) through the canonical pathway or non-canonical pathway. Activation of NF-κB results in this transcriptional factor binding with specific κB sites of different target genes. The NF-κB signaling pathway is particularly associated with liver diseases including hepatitis B virus (HBV) infection. HBV proteins have been shown to interact with different members of the NF-κB system, either enhancing or suppressing its activity. Here, we summarize current understanding on the interaction between HBV proteins and the NF-κB pathway, along with its association with liver diseases and potential therapeutic targets.

## Linked entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790], Nfkbib (nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, beta) [NCBI Gene 18036], IKKepsilon (I-kappaB kinase epsilon) [NCBI Gene 35329]
- **Diseases:** hepatitis B virus infection (MONDO:0005344)

## Full-text entities

- **Genes:** CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, TREM1 (triggering receptor expressed on myeloid cells 1) [NCBI Gene 54210] {aka CD354, TREM-1}, LTBR (lymphotoxin beta receptor) [NCBI Gene 4055] {aka D12S370, LT-BETA-R, TNF-R-III, TNFCR, TNFR-RP, TNFR2-RP}, HMGB1 (high mobility group box 1) [NCBI Gene 3146] {aka HMG-1, HMG1, HMG3, SBP-1}, VCP (valosin containing protein) [NCBI Gene 7415] {aka CDC48, FTDALS6, TERA, p97}, IKBKG (inhibitor of nuclear factor kappa B kinase regulatory subunit gamma) [NCBI Gene 8517] {aka AMCBX1, EDAID1, FIP-3, FIP3, Fip3p, IKK-gamma}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, RELB (RELB proto-oncogene, NF-kB subunit) [NCBI Gene 5971] {aka I-REL, IMD53, IREL, REL-B}, MAP3K14 (mitogen-activated protein kinase kinase kinase 14) [NCBI Gene 9020] {aka FTDCR1B, HS, HSNIK, IMD112, NIK}, CCL3 (C-C motif chemokine ligand 3) [NCBI Gene 6348] {aka G0S19-1, LD78, LD78ALPHA, MIP-1-alpha, MIP1A, SCI}, CXCL9 (C-X-C motif chemokine ligand 9) [NCBI Gene 4283] {aka CMK, Humig, MIG, SCYB9, crg-10}, Myd88 (myeloid differentiation primary response gene 88) [NCBI Gene 17874], KDM4D (lysine demethylase 4D) [NCBI Gene 55693] {aka JMJD2D}, Nfkbia (nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha) [NCBI Gene 18035] {aka Nfkbi}, HSPA5 (heat shock protein family A (Hsp70) member 5) [NCBI Gene 3309] {aka BIP, GRP78, HEL-S-89n}, REL (REL proto-oncogene, NF-kB subunit) [NCBI Gene 5966] {aka C-Rel, HIVEN86A, IMD92}, Mdk (midkine) [NCBI Gene 17242] {aka MK, Mek}, MIR1269B (microRNA 1269b) [NCBI Gene 100616494], TNFRSF6B (TNF receptor superfamily member 6b) [NCBI Gene 8771] {aka DCR3, DJ583P15.1.1, M68, M68E, TR6}, CXCL2 (C-X-C motif chemokine ligand 2) [NCBI Gene 2920] {aka CINC-2a, GRO2, GROb, MGSA-b, MIP-2a, MIP2}, PTPN11 (protein tyrosine phosphatase non-receptor type 11) [NCBI Gene 5781] {aka BPTP3, CFC, JMML, METCDS, NS1, PTP-1D}, MAP3K7 (mitogen-activated protein kinase kinase kinase 7) [NCBI Gene 6885] {aka CSCF, FMD2, MEKK7, TAK1, TGF1a}, S100A9 (S100 calcium binding protein A9) [NCBI Gene 6280] {aka 60B8AG, CAGB, CFAG, CGLB, L1AG, LIAG}, NFKBIA (NFKB inhibitor alpha) [NCBI Gene 4792] {aka EDAID2, IKBA, MAD-3, NFKBI}, IKBKB (inhibitor of nuclear factor kappa B kinase subunit beta) [NCBI Gene 3551] {aka IKK-2, IKK-beta, IKK2, IKKB, IMD15, IMD15A}, GOLM1 (golgi membrane protein 1) [NCBI Gene 51280] {aka C9orf155, GOLPH2, GP73, HEL46, PSEC0257, bA379P1.3}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, TAB2 (TGF-beta activated kinase 1 (MAP3K7) binding protein 2) [NCBI Gene 23118] {aka CHTD2, MAP3K7IP2, TAB-2}, NFKB2 (nuclear factor kappa B subunit 2) [NCBI Gene 4791] {aka CVID10, H2TF1, LYT-10, LYT10, NF-kB2, p100}, HBeAg [NCBI Gene 944568], TLR2 (toll like receptor 2) [NCBI Gene 7097] {aka CD282, TIL4}, TNFRSF13C (TNF receptor superfamily member 13C) [NCBI Gene 115650] {aka BAFF-R, BAFFR, BROMIX, CD268, CVID4, prolixin}, IL23A (interleukin 23 subunit alpha) [NCBI Gene 51561] {aka IL-23, IL-23A, IL23P19, P19, SGRF}, CFLAR (CASP8 and FADD like apoptosis regulator) [NCBI Gene 8837] {aka CASH, CASP8AP1, CLARP, Casper, FLAME, FLAME-1}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, HBx [NCBI Gene 944566], SLC7A11 (solute carrier family 7 member 11) [NCBI Gene 23657] {aka CCBR1, xCT}, TNFSF10 (TNF superfamily member 10) [NCBI Gene 8743] {aka APO2L, Apo-2L, CD253, TANCR, TL2, TNLG6A}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, HSP90AB1 (heat shock protein 90 alpha family class B member 1) [NCBI Gene 3326] {aka D6S182, HSP84, HSP90B, HSPC2, HSPCB}, SPATA2 (spermatogenesis associated 2) [NCBI Gene 9825] {aka PD1, PPP1R145, tamo}, Apoh (apolipoprotein H) [NCBI Gene 11818] {aka B2GPI, beta-2-GPI, beta2-GPI}, PHB2 (prohibitin 2) [NCBI Gene 11331] {aka BAP, BCAP37, Bap37, PNAS-141, REA, hBAP}, APOBEC3B (apolipoprotein B mRNA editing enzyme catalytic subunit 3B) [NCBI Gene 9582] {aka A3B, APOBEC1L, ARCD3, ARP4, DJ742C19.2, PHRBNL}, Polymerase [NCBI Gene 944565], TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, NKILA (NF-kappaB interacting lncRNA) [NCBI Gene 105416157], BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, HNF1A (HNF1 homeobox A) [NCBI Gene 6927] {aka HNF-1-alpha, HNF-1A, HNF1, HNF1alpha, IDDM20, LFB1}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, CHUK (component of inhibitor of nuclear factor kappa B kinase complex) [NCBI Gene 1147] {aka BPS2, IKBKA, IKK-1, IKK-alpha, IKK1, IKKA}, CD40 (CD40 molecule) [NCBI Gene 958] {aka Bp50, CDW40, TNFRSF5, p50}, TNFRSF10C (TNF receptor superfamily member 10c) [NCBI Gene 8794] {aka CD263, DCR1, DCR1-TNFR, LIT, TRAIL-R3, TRAILR3}, Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, TBK1 (TANK binding kinase 1) [NCBI Gene 29110] {aka AIARV, FTDALS4, IIAE8, NAK, T2K}, HSP90B1 (heat shock protein 90 beta family member 1) [NCBI Gene 7184] {aka ECGP, GP96, GRP94, HEL-S-125m, HEL35, TRA1}
- **Diseases:** autoimmune diseases (MESH:D001327), liver conditions (MESH:D017093), carcinogenesis (MESH:D063646), HCC (MESH:D006528), hematological malignancies (MESH:D019337), liver tumors (MESH:D008113), chronic infection (MESH:D000088562), Liver Diseases (MESH:D008107), chronic inflammation (MESH:D007249), cirrhosis (MESH:D005355), rheumatoid arthritis (MESH:D001172), metastasis (MESH:D009362), viral infection (MESH:D014777), impairment (MESH:D060825), infected (MESH:D007239), multiple myeloma (MESH:D009101), cancer (MESH:D009369), liver cirrhosis (MESH:D008103), HBV (MESH:D006509)
- **Chemicals:** Aspirin (MESH:D001241), adalimumab (MESH:D000068879), LPS (MESH:D008070), Bortezomib (MESH:D000069286), Carfilzomib (MESH:C524865), DEN (MESH:D004052), alcohol (MESH:D000438), BAY 11-7085 (MESH:C416282), infliximab (MESH:D000069285), BAY 11-7821 (-), ML120B (MESH:C514957), PGS (MESH:C528993)
- **Species:** Hepatitis B virus (no rank) [taxon 10407], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** HepAD38 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_M177), HepG2-hNTCP — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_JY40), THP-1 — Homo sapiens (Human), Childhood acute monocytic leukemia, Cancer cell line (CVCL_0006), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), HepG2.215 — Homo sapiens (Human), Induced pluripotent stem cell (CVCL_JR08), Huh7 — Homo sapiens (Human), Adult hepatocellular carcinoma, Cancer cell line (CVCL_0336), HepG2.2.15 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_L855)

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12965250/full.md

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Source: https://tomesphere.com/paper/PMC12965250