Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Nov 24:8:784172.
doi: 10.3389/fmed.2021.784172. eCollection 2021.

Suppression of Interferon-α Treatment Response by Host Negative Factors in Hepatitis B Virus Infection

Jiayi Wang  1   2 , Lingyao Du  1   2 , Hong Tang  1   2
Affiliations
Review

Suppression of Interferon-α Treatment Response by Host Negative Factors in Hepatitis B Virus Infection

Jiayi Wang et al. Front Med (Lausanne). .

Abstract

Chronic hepatitis B virus (CHB) infection remains a major global public health issue for which there is still lacking effective curative treatment. Interferon-α (IFN-α) and its pegylated form have been approved as an anti-HBV drug with the advantage of antiviral activity and host immunity against HBV infection enhancement, however, IFN-α treatment failure in CHB patients is a challenging obstacle with 70% of CHB patients respond poorly to exogenous IFN-α treatment. The IFN-α treatment response is negatively regulated by both viral and host factors, and the role of viral factors has been extensively illustrated, while much less attention has been paid to host negative factors. Here, we summarized evidence of host negative regulators and parameters involved in IFN-α therapy failure, review the mechanisms responsible for these effects, and discuss the possible improvement of IFN-based therapy and the rationale of combining the inhibitors of negative regulators in achieving an HBV cure.

Keywords: chronic hepatitis B; host factors; interferon-α; negative regulators; non-response.

PubMed Disclaimer

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
Figure 1
Type I IFN signaling is down-regulated by negative regulators. Various negative regulators cross-regulate the type I interferon (IFN) response, which modulates the expression levels and activation states of IFN signaling components. On HBV infection and invasion, pattern-recognition receptors (PRRs) recognize HBV and activate the downstream pathway to induce IFN expression. IFNAR1/2 recognize type I IFN and activate Janus kinases 1 (JAK1) and tyrosine kinase 2 (Tyk2), followed by the activation and phosphorylation of signal transducer and activator of transcription factors (STATs), leading to the expression of various IFN-stimulated genes (ISGs). Several ISGs were identified as negative regulators of the IFN signaling pathway, including the suppressor of cytokine signaling (SOCS) proteins, ubiquitin-specific protease 18 (USP18), Interferon-induced transmembrane protein 2 (IFITM2), p38 mitogen-activated kinases (p38 MAPKs), matrix metalloproteinase 9 (MMP-9), epidermal growth factor receptor (EGFR), protein tyrosine phosphatases 1 B (PTP1B), and some regulators awaiting exact mechanisms. HBV, hepatitis B virus; IRF3, IFN regulatory factor 3; IRF7, IFN regulatory factor 7; ERK1/2, extracellular signal-regulated kinase 1/2; DCs, dendritic cells.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. World Health Organization . Hepatitis B. (2021). Available online at: https://www.who.int/news-room/factsheets/detail/hepatitis-b (accessed September 25, 2021).
    1. Sagnelli E, Macera M, Russo A, Coppola N, Sagnelli C. Epidemiological and etiological variations in hepatocellular carcinoma. Infection. (2020) 48:7–17. 10.1007/s15010-019-01345-y - DOI - PubMed
    1. Tang LSY, Covert E, Wilson E, Kottilil S. Chronic Hepatitis B Infection: A Review. JAMA. (2018) 319:1802–13. 10.1001/jama.2018.3795 - DOI - PubMed
    1. Tsukuda S, Watashi K. Hepatitis B virus biology and life cycle. Antiviral Res. (2020) 182:104925. 10.1016/j.antiviral.2020.104925 - DOI - PubMed
    1. Blumberg BS, Alter HJ. A new antigen in leukemia sera. Jama. (1965) 191:541–6. 10.1001/jama.1965.03080070025007 - DOI - PubMed

LinkOut - more resources