Mechanism of interferon alpha therapy for chronic hepatitis B and potential approaches to improve its therapeutic efficacy

Zhao, Qiong; Liu, Hui; Tang, Liudi; Wang, Fuxuan; Tolufashe, Gideon; Chang, Jinhong; Guo, Ju-Tao

doi:10.1016/j.antiviral.2023.105782

Cited by 7 publications

(2 citation statements)

References 161 publications

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“…Serving as the first line of host defense, the cellular innate immune system promptly detects viral infections and triggers the production of IFNs, which, in turn, induce ISGs to restrict viral replication and propagation [ 66 , 67 ]. Despite the fact that HBV has long been considered a stealth virus capable of evading innate activation, the virus shows susceptibility to IFN treatment and a handful of ISGs [ 14 , 68 ]. Many members of the TRIM family are ISGs and play important roles in host antiviral innate immunity [ 17 , 18 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…As an obligate pathogen, HBV highly relies on the hepatic cellular machinery to complete its life cycle, but on the other hand, certain intrinsic and extrinsic host factors also restrict the replication of HBV. To date, a plethora of host restriction factors for HBV infection and reproduction have been identified under basal and/or cytokine-inducible expression conditions, representing an active area of research [ 5 , 9 , 10 , 11 , 12 , 13 , 14 ]. Therefore, it is of interest to identify additional novel host proteins that impede HBV replication at different steps of the viral life cycle, which will contribute to a comprehensive understanding of HBV–host interactions, paving the way for further mechanistic investigations and the development of potential host-targeting antiviral agents.…”

Section: Introductionmentioning

confidence: 99%

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Tripartite Motif-Containing Protein 65 (TRIM65) Inhibits Hepatitis B Virus Transcription

Shen,

Yan,

Xie

et al. 2024

Viruses

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Tripartite motif (TRIM) proteins, comprising a family of over 100 members with conserved motifs, exhibit diverse biological functions. Several TRIM proteins influence viral infections through direct antiviral mechanisms or by regulating host antiviral innate immune responses. To identify TRIM proteins modulating hepatitis B virus (HBV) replication, we assessed 45 human TRIMs in HBV-transfected HepG2 cells. Our study revealed that ectopic expression of 12 TRIM proteins significantly reduced HBV RNA and subsequent capsid-associated DNA levels. Notably, TRIM65 uniquely downregulated viral pregenomic (pg) RNA in an HBV-promoter-specific manner, suggesting a targeted antiviral effect. Mechanistically, TRIM65 inhibited HBV replication primarily at the transcriptional level via its E3 ubiquitin ligase activity and intact B-box domain. Though HNF4α emerged as a potential TRIM65 substrate, disrupting its binding site on the HBV genome did not completely abolish TRIM65’s antiviral effect. In addition, neither HBx expression nor cellular MAVS signaling was essential to TRIM65-mediated regulation of HBV transcription. Furthermore, CRISPR-mediated knock-out of TRIM65 in the HepG2-NTCP cells boosted HBV infection, validating its endogenous role. These findings underscore TRIM proteins’ capacity to inhibit HBV transcription and highlight TRIM65’s pivotal role in this process.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tripartite Motif-Containing Protein 65 (TRIM65) Inhibits Hepatitis B Virus Transcription

Shen,

Yan,

Xie

et al. 2024

Viruses

View full text Add to dashboard Cite

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Optimal Treatment Based on Interferon No Longer Makes Clinical Cure of Chronic Hepatitis B Far Away: An Evidence‐Based Review on Emerging Clinical Data

Li,

Wang,

Zhou

et al. 2024

Clin Pharma and Therapeutics

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Chronic hepatitis B (CHB) remains a major global public health problem. The functional cure is the ideal therapeutic target recommended by the latest guidelines, and pursuing a functional cure has become the key treatment end point of current therapy and for upcoming clinical trials. In this review, based on the latest published clinical research evidence, we analyzed the concept and connotation of clinical cures and elaborated on the benefits of clinical cures in detail. Secondly, we have summarized various potential treatment methods for achieving clinical cures, especially elaborating on the latest research progress of interferon‐based optimized treatment strategies in achieving clinical cures. We also analyzed which populations can achieve clinical cures and conducted a detailed analysis of relevant virological and serological markers in screening clinical cure advantage populations and predicting clinical cure achievement. In addition, we also introduced the difficulties that may be encountered in the current pursuit of achieving a clinical cure.

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The nuclear matrix protein HNRNPU restricts hepatitis B virus transcription by promoting OAS3‐based activation of host innate immunity

Zeng,

Ren,

Wang

et al. 2024

Journal of Medical Virology

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Heterogeneous nuclear protein U (HNRNPU) plays a pivotal role in innate immunity by facilitating chromatin opening to activate immune genes during host defense against viral infection. However, the mechanism by which HNRNPU is involved in Hepatitis B virus (HBV) transcription regulation through mediating antiviral immunity remains unknown. Our study revealed a significant decrease in HNRNPU levels during HBV transcription, which depends on HBx‐DDB1‐mediated degradation. Overexpression of HNRNPU suppressed HBV transcription, while its knockdown effectively promoted viral transcription, indicating HNRNPU as a novel host restriction factor for HBV transcription. Mechanistically, HNRNPU inhibits HBV transcription by activating innate immunity through primarily the positive regulation of the interferon‐stimulating factor 2′‐5′‐oligoadenylate synthetase 3, which mediates an ribonuclease L‐dependent mechanism to enhance innate immune responses. This study offers new insights into the host immune regulation of HBV transcription and proposes potential targets for therapeutic intervention against HBV infection.

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Mechanism of interferon alpha therapy for chronic hepatitis B and potential approaches to improve its therapeutic efficacy

Cited by 7 publications

References 161 publications

Tripartite Motif-Containing Protein 65 (TRIM65) Inhibits Hepatitis B Virus Transcription

Tripartite Motif-Containing Protein 65 (TRIM65) Inhibits Hepatitis B Virus Transcription

Optimal Treatment Based on Interferon No Longer Makes Clinical Cure of Chronic Hepatitis B Far Away: An Evidence‐Based Review on Emerging Clinical Data

The nuclear matrix protein HNRNPU restricts hepatitis B virus transcription by promoting OAS3‐based activation of host innate immunity

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