The Functions of Hepatitis B Virus Encoding Proteins: Viral Persistence and Liver Pathogenesis

Zhao, Feiyang; Xie, Xiaoyu; Tan, Xu; Yu, Hongli; Tian, Miaomiao; Lv, Huanran; Qin, Chengyong; Qi, Jianni; Zhu, Qiang

doi:10.3389/fimmu.2021.691766

Cited by 49 publications

(33 citation statements)

References 134 publications

(191 reference statements)

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“…A significant factor contributing to chronic HBV infection is a functional defect in the adaptive immune response, specifically the HBV‐specific T‐cell response 81 . Continuous, unabated exposure to the viral proteins HBcAg, HBeAg, HBX, HBV polymerase and in particular HBsAg 82 leads to T‐cell exhaustion and upregulation of co‐inhibitory molecules such as programmed cell death protein 1 (PD1), 83 cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4) 84 and T cell immunoglobulin and mucin domain 3 (Tim‐3) 85 . Thus, blockade of these receptors could potentially restore the HBV‐specific T‐cell response.…”

Section: Targeting the Adaptive Immune Systemmentioning

confidence: 99%

Review article: hepatitis B—current and emerging therapies

Yardeni

Ghany

2022

Aliment Pharmacol Ther

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Background The hepatitis B virus (HBV) affects an estimated 290 million individuals worldwide and is responsible for approximately 900 000 deaths annually, mostly from complications of cirrhosis and hepatocellular carcinoma. Although current treatment is effective at preventing complications of chronic hepatitis B, it is not curative, and often must be administered long term. There is a need for safe, effective, finite duration curative therapy. Aim Our aim was to provide a concise, up to date review of all currently available and emerging treatment options for chronic hepatitis B. Methods We conducted a search of PubMed, clinicaltrials.gov, major meeting abstracts and pharmaceutical websites for publications and communications on current and emerging therapies for HBV. Results Currently approved treatment options for chronic hepatitis B include peginterferon alpha‐2a and nucleos(t)ide analogues. Both options do not offer a ‘complete cure’ (clearance of covalently closed circular DNA (cccDNA) and integrated HBV DNA) and rarely achieve a ‘functional cure’ (hepatitis B surface antigen (HBsAg) loss). An improved understanding of the viral lifecycle, immunopathogenesis and recent advances in drug delivery technologies have led to many novel therapeutic approaches that are currently being evaluated in clinical trials including targeting of viral entry, cccDNA, viral transcription, core protein, and release of HBsAg and HBV polymerase. Additionally, novel immunological approaches that include targeting the innate and adaptive immune system and therapeutic vaccination are being pursued. Conclusion The breadth and scope of novel therapies in development hold promise for regimen/s that will achieve functional cure.

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Section: Targeting the Adaptive Immune Systemmentioning

confidence: 99%

Review article: hepatitis B—current and emerging therapies

Yardeni

Ghany

2022

Aliment Pharmacol Ther

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“…HOXA13 thereafter binds to the HBV enhancer 1 and X promoter to restrain viral replication. In this manner, HBV polymerase negatively regulates replication, possibly to avoid host immune responses, and establish chronicity [reviewed in (65)].…”

Section: Hottipmentioning

confidence: 99%

Diversity of Dysregulated Long Non-Coding RNAs in HBV-Related Hepatocellular Carcinoma

et al. 2022

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Infection with the hepatitis B virus (HBV) continues to pose a major threat to public health as approximately 292 million people worldwide are currently living with the chronic form of the disease, for which treatment is non-curative. Chronic HBV infections often progress to hepatocellular carcinoma (HCC) which is one of the world’s leading causes of cancer-related deaths. Although the process of hepatocarcinogenesis is multifaceted and has yet to be fully elucidated, several studies have implicated numerous long non-coding RNAs (lncRNAs) as contributors to the development of HCC. These host-derived lncRNAs, which are often dysregulated as a consequence of viral infection, have been shown to function as signals, decoys, guides, or scaffolds, to modulate gene expression at epigenetic, transcriptional, post-transcriptional and even post-translational levels. These lncRNAs mainly function to promote HBV replication and oncogene expression or downregulate tumor suppressors. Very few lncRNAs are known to suppress tumorigenesis and these are often downregulated in HCC. In this review, we describe the mechanisms by which lncRNA dysregulation in HBV-related HCC promotes tumorigenesis and cancer progression.

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“…S ORF contributes to the production of large, middle, and small envelope proteins that are composed of HBsAg, preS1, or preS2 antigens; P and C ORFs encode the HBV polymerase protein, core protein, and HBeAg. Additionally, X ORF is responsible for the expression of HBX, a highly conserved nonstructural protein with 154-amino acids (17)(18)(19). Based on the studies on cell and mouse models, HBX is considered to be important for initiating and maintaining HBV replication (20,21).…”

Section: Introductionmentioning

confidence: 99%

Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection

et al. 2022

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As a small DNA virus, hepatitis B virus (HBV) plays a pivotal role in the development of various liver diseases, including hepatitis, cirrhosis, and liver cancer. Among the molecules encoded by this virus, the HBV X protein (HBX) is a viral transactivator that plays a vital role in HBV replication and virus-associated diseases. Accumulating evidence so far indicates that pattern recognition receptors (PRRs) are at the front-line of the host defense responses to restrict the virus by inducing the expression of interferons and various inflammatory factors. However, depending on HBX, the virus can control PRR signaling by modulating the expression and activity of essential molecules involved in the toll-like receptor (TLR), retinoic acid inducible gene I (RIG-I)-like receptor (RLR), and NOD-like receptor (NLR) signaling pathways, to not only facilitate HBV replication, but also promote the development of viral diseases. In this review, we provide an overview of the mechanisms that are linked to the regulation of PRR signaling mediated by HBX to inhibit innate immunity, regulation of viral propagation, virus-induced inflammation, and hepatocarcinogenesis. Given the importance of PRRs in the control of HBV replication, we propose that a comprehensive understanding of the modulation of cellular factors involved in PRR signaling induced by the viral protein may open new avenues for the treatment of HBV infection.

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The Functions of Hepatitis B Virus Encoding Proteins: Viral Persistence and Liver Pathogenesis

Cited by 49 publications

References 134 publications

Review article: hepatitis B—current and emerging therapies

Review article: hepatitis B—current and emerging therapies

Diversity of Dysregulated Long Non-Coding RNAs in HBV-Related Hepatocellular Carcinoma

Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection

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