scholarly journals Hepatitis B Virus (HBV) - Induced Hepatocarcinogenesis, a Founding Framework of Cancer Evolution & Development (Cancer Evo-Dev)

2021 ◽  
Author(s):  
Wenbin Liu ◽  
Guangwen Cao
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Inflammatory Factors ◽  
Cancer Evolution ◽  
Uracil Dna Glycosylase ◽  
Cytidine Deaminases ◽  
Inflammatory Microenvironment ◽  
B Virus ◽  
Novel Theory ◽  
And Function

In this chapter, we present the founding framework of a novel theory termed as Cancer Evolution-Development (Cancer Evo-Dev), based on the current understanding of hepatitis B virus (HBV) induced hepatocarcinogenesis. The interactions of genetic predispositions and HBV infection is responsible for the maintenance of chronic non-resolving inflammation. Under the inflammatory microenvironment, pro-inflammatory factors trans-activate the expression of cytidine deaminases and suppress the expression of uracil DNA glycosylase. The imbalance between the mutagenic forces and mutation-correcting forces facilitates the generations of somatic mutations, viral mutations, and viral integrations into the host genomes. The majority of cells with genomic mutations and mutated viruses are eliminated in survival competition. Only a small percentage of the mutated cells adapted to the hostile environment can survive, retro-differentiate, and function as cancer-initiating cells, representing a process of “mutation-selection-adaptation”. Cancer Evo-Dev lays the theoretical foundation for understanding the mechanisms by which chronic infection of HBV promotes hepatocarcinogenesis. This theory also plays an important role in specific prophylaxis, prediction, early diagnosis, and targeted treatment of cancers.

The high expression of the pain-related inflammatory factors in the eyes of cataract patients infected with hepatitis B virus

Cytokine ◽  
2020 ◽  
Vol 134 ◽  
pp. 155189
Author(s):  
Jing Shang Zhang ◽  
Jin Da Wang ◽  
Gu Yu Zhu ◽  
Mayinuer Yusufu ◽  
Ying Xiong ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
High Expression ◽  
Inflammatory Factors ◽  
B Virus ◽  
Cataract Patients

Over IFI16 expression increased inflammation in Hepatitis B Virus-Associated Glomerulonephritis by Regulating Caspase-1 and IL-1 ß

2020 ◽  
Author(s):  
zhaoqing zeng ◽  
yuyang li ◽  
jinhong yu ◽  
jing liu ◽  
shijun chen ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Cell Line ◽  
Renal Damage ◽  
Hbv Infection ◽  
Inflammatory Factors ◽  
Inflammasome Activation ◽  
Caspase 1 ◽  
B Virus

Abstract Aims & background: IFI16 plays an important role in innate immunity against invasive microbial infection by sensing double-stranded DNA viruses due to caspase-1-dependent inflammasome activation and subsequent maturation and secretion of IL-1β. However, the role of IFI16 in regulating the immune response to viruses in vivo and in vitro, especially in sensing hepatitis B virus (HBV), has not been examined. We hypothesized that the expression of IFI16 increases corresponding to HBV-mediated inflammation in patients with hepatitis B virus associated glomerulonephritis (HBV-GN), a condition which activates inflammatory mechanisms and causes renal damage. To test this hypothesis, we therefore analyzed the expression of IFI16 and inflammatory factors in HBV-GN tissues and cell lines relative to the inflammatory response to HBV infection. Methods: A total 75 patients with chronic nephritis(CN) including 50 with HBV-GN and 25 with chronic glomerulonephritis (CCN) involved in this study. Each CN patient received renal biopsy, and immunohistochemistry(IHC) was used to detect the expression of IFI16 and inflammatory factors Caspase-1 and IL-1β in the biopsy specimens. Following IFI16 was transfected in HBV-infected and HBV-uninfected human glomerular mesangial (HGM) cell line and HEK-293T cell line, expression of Caspase-1 and IL-1β were detected by Western blot and qRT- PCR. Results: IFI16 expression in HBV-GN biopsies (80.0%) was significantly higher than in CGN (24.0%) and positively correlated with caspase-1 and IL-1𝛽 expression in HBV-GN. In vitro, over expression IFI16 increased caspase-1 and IL-1𝛽 expression in HBV -infected HGM and HEK-293T. Conclusions: The elevation of IFI16 during HBV infection or replication may contribute to renal damage due to inflammation, thus providing a putative therapeutic target and a new avenue for researching the pathogenesis of HBV-GN.

scholarly journals Structural and biochemical analysis of Bcl-2 interaction with the hepatitis B virus protein HBx

2016 ◽  
Vol 113 (8) ◽  
pp. 2074-2079 ◽  
Author(s):  
Tianyu Jiang ◽  
Minhao Liu ◽  
Jianping Wu ◽  
Yigong Shi
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Virus Protein ◽  
B Virus ◽  
Iron And Zinc ◽  
Important Host ◽  
Binding Groove ◽  
Α Helix ◽  
And Function

HBx is a hepatitis B virus protein that is required for viral infectivity and replication. Anti-apoptotic Bcl-2 family members are thought to be among the important host targets of HBx. However, the structure and function of HBx are poorly understood and the molecular mechanism of HBx-induced carcinogenesis remains unknown. In this study, we report biochemical and structural characterization of HBx. The recombinant HBx protein contains metal ions, in particular iron and zinc. A BH3-like motif in HBx (residues 110–135) binds Bcl-2 with a dissociation constant of ∼193 μM, which is drastically lower than that for a canonical BH3 motif from Bim or Bad. Structural analysis reveals that, similar to other BH3 motifs, the BH3-like motif of HBx adopts an amphipathic α-helix and binds the conserved BH3-binding groove on Bcl-2. Unlike the helical Bim or Bad BH3 motif, the C-terminal portion of the bound HBx BH3-like motif has an extended conformation and makes considerably fewer interactions with Bcl-2. These observations suggest that HBx may modulate Bcl-2 function in a way that is different from that of the classical BH3-only proteins.

scholarly journals Interplay Between Non-Canonical NF-κB Signaling and Hepatitis B Virus Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinyu Lu ◽  
Qianhui Chen ◽  
Hongyan Liu ◽  
Xiaoyong Zhang
Keyword(s):  
Immune System ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Signaling Pathway ◽  
Hbv Infection ◽  
Host Immune System ◽  
Novel Drugs ◽  
B Virus ◽  
And Function ◽  
Light Chain Enhancer

The non-canonical nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway is an important component of NF-κB transcription complex. Activation of this pathway mediates the development and function of host immune system involved in inflammation and viral infection. During hepatitis B virus (HBV) infection, there is a complex interaction between infected hepatocytes and the immune cells, which can hinder antiviral immune responses and is associated with pathological changes in liver tissue. Consistently, the host immune system is closely related to the severity of liver damage and the level of viral replication. Previous studies indicated that the non-canonical NF-κB signaling pathway was affected by HBV and might play an important regulatory role in the antiviral immunity. Therefore, systematically elucidating the interplay between HBV and non-canonical NF-κB signaling will contribute the discovery of more potential therapeutic targets and novel drugs to treat HBV infection.

scholarly journals Cancer Evo–Dev: A Theory of Inflammation-Induced Oncogenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenbin Liu ◽  
Yang Deng ◽  
Zishuai Li ◽  
Yifan Chen ◽  
Xiaoqiong Zhu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Somatic Mutations ◽  
Inflammatory Factors ◽  
Low Grade ◽  
Cancer Evolution ◽  
Effective Prophylaxis ◽  
Novel Theory ◽  
And Function ◽  
Carcinogenic Process ◽  
Risk Of Cancer

Chronic inflammation is a prerequisite for the development of cancers. Here, we present the framework of a novel theory termed as Cancer Evolution-Development (Cancer Evo-Dev) based on the current understanding of inflammation-related carcinogenesis, especially hepatocarcinogenesis induced by chronic infection with hepatitis B virus. The interaction between genetic predispositions and environmental exposures, such as viral infection, maintains chronic non-resolving inflammation. Pollution, metabolic syndrome, physical inactivity, ageing, and adverse psychosocial exposure also increase the risk of cancer via inducing chronic low-grade smoldering inflammation. Under the microenvironment of non-resolving inflammation, pro-inflammatory factors facilitate the generation of somatic mutations and viral mutations by inducing the imbalance between the mutagenic forces such as cytidine deaminases and mutation-correcting forces including uracil–DNA glycosylase. Most cells with somatic mutations and mutated viruses are eliminated in survival competition. Only a small percentage of mutated cells survive, adapt to the hostile environment, retro-differentiate, and function as cancer-initiating cells via altering signaling pathways. These cancer-initiating cells acquire stem-ness, reprogram metabolic patterns, and affect the microenvironment. The carcinogenic process follows the law of “mutation-selection-adaptation”. Chronic physical activity reduces the levels of inflammation via upregulating the activity and numbers of NK cells and lymphocytes and lengthening leukocyte telomere; downregulating proinflammatory cytokines including interleukin-6 and senescent lymphocytes especially in aged population. Anti-inflammation medication reduces the occurrence and recurrence of cancers. Targeting cancer stemness signaling pathways might lead to cancer eradication. Cancer Evo-Dev not only helps understand the mechanisms by which inflammation promotes the development of cancers, but also lays the foundation for effective prophylaxis and targeted therapy of various cancers.

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