Interplay Between Non-Canonical NF-κB Signaling and Hepatitis B Virus Infection - PubMed (original) (raw)

Review

Interplay Between Non-Canonical NF-κB Signaling and Hepatitis B Virus Infection

Xinyu Lu et al. Front Immunol. 2021.

Abstract

The non-canonical nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway is an important component of NF-κB transcription complex. Activation of this pathway mediates the development and function of host immune system involved in inflammation and viral infection. During hepatitis B virus (HBV) infection, there is a complex interaction between infected hepatocytes and the immune cells, which can hinder antiviral immune responses and is associated with pathological changes in liver tissue. Consistently, the host immune system is closely related to the severity of liver damage and the level of viral replication. Previous studies indicated that the non-canonical NF-κB signaling pathway was affected by HBV and might play an important regulatory role in the antiviral immunity. Therefore, systematically elucidating the interplay between HBV and non-canonical NF-κB signaling will contribute the discovery of more potential therapeutic targets and novel drugs to treat HBV infection.

Keywords: NF-κB-inducing kinase (NIK); antiviral immunity; hepatitis B virus (HBV); non-canonical NF-κB signaling; p100/p52 (NFKB2).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1

Activation of canonical NF-κB signaling and non-canonical NF-κB signaling. (A) Canonical NF-κB signaling is stimulated by proinflammatory cytokines such as IL-1β, TNF-α and LPS, inducing the activation of IKK complex by TAK1. The IKK complex then phosphorylates the IκB kinase α/β (IKKα/β), causing the ubiquitin-dependent degradation of κB inhibitory factors (IκBs) protein, thereby triggering the nuclear transcription factor heterodimer RelA/p50. (B) Non-canonical NF-κB signaling is activated by the specific TNFR superfamily. Receptor activation induce the recruitment of TRAF3-TRAF2-cIAP1/2 receptor complex, followed by the degradation of TRAF3 via ubiquitination, resulting in the stabilization and accumulation of NIK. NIK phosphorylates IKKα which in turn phosphorate p100, triggering the ubiquitination and degradation of p100 to generate p52 and the nuclear transduction of RelB-p52 heterodimer.

Figure 2

Non-canonical NF-κB signaling pathway regulates the HBV infection. (A) In hepatocyte, activation of LTB receptor in hepatocyte mediates the non-canonical NF-κB signaling pathway and induce the up-regulated expression of APOBCE3A/B protein, which degrade cccDNA. (B) Targeting cIAPs also mediate the activating the NIK-dependent non-canonical NF-κB signaling pathway and exert the antiviral effect in hepatocyte via TNF-mediated death of infected cells. (C, D) Specific ligation of OX40, BAFFR or CD40 in immune cells might recover the exhausted immune function during HBV infection through the activation of the NIK-dependent non-canonical NF-κB signaling pathway.

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Interplay Between Non-Canonical NF-κB Signaling and Hepatitis B Virus Infection - PubMed (original) (raw)