HBV Infection and Host Interactions: The Role in Viral Persistence and Oncogenesis

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7651 - 7651

Published: April 21, 2023

Hepatitis B virus (HBV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Despite the advent vaccines potent antiviral agents able to suppress viral replication, recovery from HBV infection still an extremely difficult goal achieve. Complex interactions between host are responsible for persistence risk oncogenesis. Through multiple pathways, silence both innate adaptive immunological responses become out control. Furthermore, integration genome into that production covalently closed circular DNA (cccDNA) represent reservoirs account eradication infection. An adequate knowledge virus–host interaction mechanisms hepatocarcinogenesis necessary development functional cures The purpose this review is, therefore, analyze how concur in infection, persistence, oncogenesis what implications therapeutic perspectives follow.

Language: Английский

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Elimination of the hepatitis B virus: A goal, a challenge

Medicinal Research Reviews, Journal Year: 2024, Volume and Issue: 44(5), P. 2015 - 2034

Published: March 25, 2024

Abstract The hepatitis B elimination is a goal proposed by the WHO to be achieved 2030 through adoption of synergistic measures for prevention and chronic HBV infection treatment. Complete cure characterized from body treatment, which once achieved, will enable elimination. This, today, has been scientific challenge. difficulty in achieving complete due indefinite maintenance covalently closed episomal circular DNA (cccDNA) reservoir persistence an insufficient dysfunctional immune response chronically infected patients. Among adopted eliminate B, two have potential directly interfere with virus cycle, but limited effect on control. These are conventional vaccines—blocking transmission antiviral therapy—inhibiting replication. Vaccines, despite their effectiveness protecting against horizontal preventing mother‐to‐child vertical transmission, no or virus. Treatment antivirals suppresses viral replication, curative effect, as it action cccDNA. Therapeutic vaccines comprise additional approach however, they only modest system, enhancing temporarily. This manuscript aims address (1) cccDNA hepatocyte nucleus dysfunction individuals primary factors that hampered treatment human body; (2) limitations therapy therapeutic vaccines, strategies control B; (3) possibly promising approaches B.

Language: Английский

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Host and HBV Interactions and Their Potential Impact on Clinical Outcomes

Pathogens, Journal Year: 2023, Volume and Issue: 12(9), P. 1146 - 1146

Published: Sept. 8, 2023

Hepatitis B virus (HBV) is a challenge for global health services, affecting millions and leading thousands to end-stage liver disease each year. This comprehensive review explores the interactions between HBV host, examining their impact on clinical outcomes. infection encompasses spectrum of severity, ranging from acute hepatitis chronic B, which can potentially progress cirrhosis hepatocellular carcinoma (HCC). Occult (OBI), characterized by low DNA levels in surface antigen-negative individuals, reactivate cause B. genotyping has revealed unique geographical patterns relationships with Moreover, single nucleotide polymorphisms (SNPs) within human host genome have been linked several outcomes, including cirrhosis, HCC, OBI, reactivation, spontaneous clearance. The immune response plays key role controlling eliminating infected cells neutralizing bloodstream. Furthermore, modulate metabolic pathways involved glucose lipid metabolism bile acid absorption, influencing progression. outcomes correlate three viral adaptation. In conclusion, could result complex HBV. These vary among populations are influenced genotypes, genetics, environmental factors, lifestyle. Understanding degrees adaptation essential developing region-specific control prevention measures.

Language: Английский

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Role of hepatitis B virus non-structural protein HBx on HBV replication, interferon signaling, and hepatocarcinogenesis

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Dec. 21, 2023

Hepatitis B, a global health concern caused by the hepatitis B virus (HBV), infects nearly 2 billion individuals worldwide, as reported World Health Organization (WHO). HBV, hepatotropic DNA virus, predominantly targets and replicates within hepatocytes. Those carrying are at increased risk of liver cirrhosis hepatocellular carcinoma, resulting in 900,000 fatalities annually. The HBV X protein (HBx), encoded virus’s open reading frame x, plays key role its virulence. This is integral to viral replication, immune modulation, cancer progression. Despite significance, precise molecular mechanisms underlying HBx remain elusive. review investigates protein’s roles interferon signaling regulation, carcinoma By understanding complex interactions between host mediated HBx, we aim establish solid foundation for future research development HBx-targeted therapeutics.

Language: Английский

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The combination of Schisandrin C and Luteolin synergistically attenuates hepatitis B virus infection via repressing HBV replication and promoting cGAS-STING pathway activation in macrophages

Chinese Medicine, Journal Year: 2024, Volume and Issue: 19(1)

Published: March 18, 2024

Abstract Background HBV infection can result in severe liver diseases and is one of the primary causes cell carcinoma-related mortality. Liuwei Wuling tablet (LWWL) a traditional Chinese medicine formula, with protecting decreasing enzyme activity, usually used to treat chronic hepatitis B NAs clinic. However, its main active ingredients mechanism action have not been fully investigated. Hence, we aimed screen ingredient effective combinations from explore anti-herpatitis virus activity mechanism. Methods Analysis screening antiviral components LWWL by network pharmacology, luteolin (Lut) may be compound significant activity. The Lut was also found real-time PCR detection western blotting. Meanwhile, established co-culture model investigate Schisandrin C (SC), Schisandra chinensis fructus (the sovereign drug LWWL). Next, HBV-infected mice were tail vein injection pAAV-HBV1.2 plasmid administered continuously for 20 days. And their capacity evaluated checking serum levels HBsAg, HBeAg, DNA, HBcAg. Results In this study, conducted pharmacology analysis on LWWL, through vitro experimental validation data analysis, that possessed obviously anti-HBV inhibiting replication downregulating hepatocyte nuclear factor 4α (HNF4α) via ERK pathway. Additionally, system proved SC promoted activation cGAS-STINIG pathway IFN-β production THP-1 cells inhibit HepG2.2.15 cells. Moreover, combination shows greater effect compared or alone mice. Conclusion Taken together, our study suggests potential candidate prevention treatment B.

Language: Английский

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The impact of integrated hepatitis B virus DNA on oncogenesis and antiviral therapy

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Aug. 15, 2024

Abstract The global burden of hepatitis B virus (HBV) infection remains high, with chronic (CHB) patients facing a significantly increased risk developing cirrhosis and hepatocellular carcinoma (HCC). ultimate objective antiviral therapy is to achieve sterilizing cure for HBV. This necessitates the elimination intrahepatic covalently closed circular DNA (cccDNA) complete eradication integrated HBV DNA. review aims summarize oncogenetic role integration significance clearing in cure. It specifically focuses on molecular mechanisms through which leads HCC, including modulation expression proto-oncogenes tumor suppressor genes, induction chromosomal instability, truncated mutant proteins. also highlights impact reducing preventing HBV-related HCC. Additionally, offers insights into future objectives treatment CHB. Current strategies inhibition include mainly therapies, RNA interference gene editing technologies. Overall, deserves further investigation can potentially serve as biomarker CHB

Language: Английский

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Multi-omics landscape of Interferon-stimulated gene OASL reveals a potential biomarker in pan-cancer: from prognosis to tumor microenvironment

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 2, 2024

Background OASL (Oligoadenylate Synthetase-Like), an interferon-induced protein in the OAS family, plays a significant role anti-viral response. Studies have demonstrated its association with prognosis of certain tumors. However, mechanism through which affects tumors is unclear. A systemic pan-cancer study needs to be illustrated. Methods Analysis expression across 33 was conducted utilizing TCGA, GTEx and CPTAC databases. COX Log-Rank regressions were employed calculate prognosis. We validated impact on apoptosis, migration, invasion pancreatic cancer cell lines. Moreover, we seven algorithms bulk data investigate immune infiltration within tumor microenvironment (TIME) ultimately at single-cell transcriptome level. Results discovered elevated genetic heterogeneity tumors, link closely Validation experiments PAAD confirmed these findings. Additionally, regulates checkpoint ligand such as programmed death 1 (PD-L1), IFN-γ/STAT1 IL-6/JAK/STAT3 pathways cells. Meanwhile, macrophages TIME. By mechanisms could cause dysfunction cytotoxic T lymphocytes (CTLs) Discussion Multi-omics analysis reveals prognostic immunological biomarker pan-cancer.

Language: Английский

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Ethanol Disrupts the Protective Crosstalk Between Macrophages and HBV-Infected Hepatocytes

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 57 - 57

Published: Jan. 3, 2025

About 296 million people worldwide are living with chronic hepatitis B viral (HBV) infection, and outcomes to end-stage liver diseases potentiated by alcohol. HBV replicates in hepatocytes, but other non-parenchymal cells can sense the virus. In this study, we aimed investigate regulatory effects of macrophages on marker interferon-stimulated genes (ISGs) expressions hepatocytes. This study was performed HBV-replicating HepG2.2.15 human monocyte-derived (MDMs). We found that exposure an acetaldehyde-generating system (AGS) increased RNA, DNA, cccDNA suppressed activation ISGs, APOBEC3G, ISG15, OAS1. Supernatants collected from IFNα-activated MDMs decreased levels induced ISG AGS-treated untreated HepG2.215 cells. These were reversed ethanol mimicked treatment exosome release inhibitor GW4869. conclude exosome-mediated crosstalk between IFN-activated hepatocytes plays a protective role via up-regulation ISGs suppression replication. However, breaks protection.

Language: Английский

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Global stability analysis of a nested multiscale model for intracellular and intercellular dynamics

Advances in Continuous and Discrete Models, Journal Year: 2025, Volume and Issue: 2025(1)

Published: April 15, 2025

Language: Английский

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Exploiting Host Kinases to Combat Dengue Virus Infection and Disease

Antiviral Research, Journal Year: 2025, Volume and Issue: unknown, P. 106172 - 106172

Published: May 1, 2025

Language: Английский

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