Novel Molecular Therapeutics Targeting Signaling Pathway to Control Hepatitis B Viral Infection

Yan, Yan; Qiu, Yuanwang; Davgadorj, Chantsalmaa; Zheng, Chunfu

doi:10.3389/fcimb.2022.847539

Cited by 10 publications

(3 citation statements)

References 105 publications

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“…The two primary classes of anti-hepatitis B virus medications now available are nucleoside (acid) and interferon medications [54,55] . The former can prevent HBV replication by competing for binding with viral DNA polymerase and incorporating it into the expanding DNA strand to stop the synthesis of new strands irreversibly.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: TRPV4 promotes HBV replication and capsid assembly via methylation modification of H3K4 and HBc ubiquitin

Zhang,

Yuan,

Wang

et al. 2023

Preprint

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Background Hepatitis B virus (HBV) infection poses a significant burden on global public health. Unfortunately, current treatments cannot fully alleviate this burden as they have limited effect on the transcriptional activity of the tenacious covalently closed circular DNA (cccDNA) responsible for viral persistence. Consequently, the HBV life cycle should be further investigated to develop new anti-HBV pharmaceutical targets. Our previous study discovered that the host gene TMEM203 hinders HBV replication by participating in calcium ion regulation. The involvement of intracellular calcium in HBV replication has also been confirmed. Results In this study, we found that transient receptor potential vanilloid 4 (TRPV4) notably enhances HBV reproduction by investigating the effects of several calcium ion-related molecules on HBV replication. The in-depth study showed that TRPV4 promotes hepatitis B core/capsid protein (HBc) protein stability through the ubiquitination pathway and then promotes the nucleocapsid assembly. HBc binds to cccDNA and reduces the nucleosome spacing of the cccDNA-histones complex, which may regulate HBV transcription by altering the nucleosome arrangement of the HBV genome. Moreover, our results showed that TRPV4 promotes cccDNA-dependent transcription by accelerating the methylation modification of H3K4. In conclusion, TRPV4 could interact with HBV core protein and regulate HBV during transcription and replication. Conclusions These data suggest that TRPV4 exerts multifaceted HBV-related synergistic factors and may serve as a therapeutic target for CHB.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: TRPV4 promotes HBV replication and capsid assembly via methylation modification of H3K4 and HBc ubiquitin

Zhang,

Yuan,

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…The two primary classes of anti-HBV medications now available are nucleoside (acid) and interferon medications. 60,61 The former can prevent HBV replication by competing for binding with viral DNA polymerase and incorporating it into the expanding DNA strand to stop the synthesis of new strands irreversibly. The latter affects immunity or hosts proteins in infected hepatocytes to exert antiviral effects.…”

Section: Discussionmentioning

confidence: 99%

TRPV4 promotes HBV replication and capsid assembly via methylation modification of H3K4 and HBc ubiquitin

Zhang,

Yuan,

Wang

et al. 2024

Journal of Medical Virology

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Hepatitis B virus (HBV) infection poses a significant burden on global public health. Unfortunately, current treatments cannot fully alleviate this burden as they have limited effect on the transcriptional activity of the tenacious covalently closed circular DNA (cccDNA) responsible for viral persistence. Consequently, the HBV life cycle should be further investigated to develop new anti‐HBV pharmaceutical targets. Our previous study discovered that the host gene TMEM203 hinders HBV replication by participating in calcium ion regulation. The involvement of intracellular calcium in HBV replication has also been confirmed. In this study, we found that transient receptor potential vanilloid 4 (TRPV4) notably enhances HBV reproduction by investigating the effects of several calcium ion‐related molecules on HBV replication. The in‐depth study showed that TRPV4 promotes hepatitis B core/capsid protein (HBc) protein stability through the ubiquitination pathway and then promotes the nucleocapsid assembly. HBc binds to cccDNA and reduces the nucleosome spacing of the cccDNA‐histones complex, which may regulate HBV transcription by altering the nucleosome arrangement of the HBV genome. Moreover, our results showed that TRPV4 promotes cccDNA‐dependent transcription by accelerating the methylation modification of H3K4. In conclusion, TRPV4 could interact with HBV core protein and regulate HBV during transcription and replication. These data suggest that TRPV4 exerts multifaceted HBV‐related synergistic factors and may serve as a therapeutic target for CHB.

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“…Human consumable cytokines and growth factors were mainly used during that period. With the advent of science, it has been shown that toll-like receptors (TLRs) represent the initial sensors of microbial infection, and stimulation of TLR by viruses may result in cellular and molecular events that induce various antiviral mediators [ 52 , 53 ]. Thus, one of the notable modes of HBV suppression may be mediated and accelerated using TLR agonists.…”

Section: Hbv-antigen Non-specific Immune Therapy Using Polyclonal Imm...mentioning

confidence: 99%

Immune therapies against chronic hepatitis B

2022

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Patients with chronic hepatitis B (CHB) represent a living and permanent reservoir of hepatitis B virus (HBV). Millions of these CHB patients will eventually develop complications such as liver cirrhosis, hepatic failure, and hepatocellular carcinoma if they are not treated properly. Accordingly, several antiviral drugs have been developed for the treatment of CHB, but these drugs can neither eradicate all forms of HBV nor contain the progression of complications in most patients with CHB. Thus, the development of new and novel therapeutics for CHB remains a pressing need. The molecular and cellular mechanisms underlying the pathogenesis of CHB indicate that immune dysregulations may be responsible for HBV persistence and progressive liver damage in CHB. This provided the scientific and ethical basis for the immune therapy of CHB patients. Around 30 years have passed since the initiation of immune therapies for CHB in the early 1990s, and hundreds of clinical trials have been accomplished to substantiate this immune treatment. Despite these approaches, an acceptable regimen of immune therapy is yet to be realized. However, most immune therapeutic agents are safe for human usage, and many of these protocols have inspired considerable optimism. In this review, the pros and cons of different immune therapies, observed in patients with CHB during the last 30 years, will be discussed to derive insights into the development of an evidence-based, effective, and patient-friendly regimen of immune therapy for the treatment of CHB.

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Novel Molecular Therapeutics Targeting Signaling Pathway to Control Hepatitis B Viral Infection

Cited by 10 publications

References 105 publications

WITHDRAWN: TRPV4 promotes HBV replication and capsid assembly via methylation modification of H3K4 and HBc ubiquitin

WITHDRAWN: TRPV4 promotes HBV replication and capsid assembly via methylation modification of H3K4 and HBc ubiquitin

TRPV4 promotes HBV replication and capsid assembly via methylation modification of H3K4 and HBc ubiquitin

Immune therapies against chronic hepatitis B

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