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Cancer-Causing Viruses
Published in Satya Prakash Gupta, Cancer-Causing Viruses and Their Inhibitors, 2014
Satya P. Gupta, Vertika Gautam
HBV-associated liver carcinogenesis is thought to be a multifactorial process in which the mutations in core protein preS of HBV lead to immune modulation; HBx leads to apoptosis regulation and proliferation; and preS mutation followed by HBx action leads to genetic instability. Further studies are, however, necessary to find the molecular mechanisms for the development of HBV-associated HCC.
Lymphoma of the liver
Published in Franco Cavalli, Harald Stein, Emanuele Zucca, Extranodal Lymphomas, 2008
Christoph Loddenkemper, Thomas Longerich
Primary hepatic lymphomas have been described in association with chronic liver diseases, although there is no direct experimental evidence supporting a pathogenic link. Beside their hepatotropism, the HBV as well as the HCV have been demonstrated to be also lymphotropic.23,24 Epidemiological data show an increased prevalence (9–50%) of chronic HBV and HCV infection in patients suffering from NHL.11,15,25–27 Similar to hepato-carcinogenesis, both HBV integration and HBx-mediated transactivation may be involved in HBV-associated lymphogenesis, but experimental evidence is missing. HCV-associated lymphomagenesis has been attributed to chronic B-cell stimulation and some authors have hypothesized that HCV-associated cryoglobulinemia may be a precursor stage in this regard. Additionally, a translocation t(14;18) involving the BCL2 gene has been detected in some chronically HCV-infected patients.28–30 Casuistically, primary hepatic lymphomas have been described in association with genetic hemochromatosis.31,32
Genetics of liver cancer
Published in J. K. Cowell, Molecular Genetics of Cancer, 2003
A.-M. Hui, L. Sun, M. Makuuchi
Extensive epidemiological evidence indicates that most HCCs are associated with hepatitis B virus (HBV) or HCV infection. In China and Southeast Asia, HBV is highly prevalent and accounts for more than 60% of HCC cases. In Japan, Italy and Spain, HCV infection is the major culprit and is responsible for more than 60% of HCC cases (Okuda, 1997). In this latter group of countries, HBV appears to play a relatively minor role, being involved in perhaps fewer than 25% of HCC cases. Direct evidence for the causal role of HBV in HCC comes from the fact that HBV DNA sequences can be detected in the cellular DNA in HBV-related HCCs (Brechot et al., 1980), while a segment of HBV DNA called HBx, which encodes a transcription factor, can induce liver tumors in transgenic mice (Kim et al., 1991). HCV is not integrated into the host cell DNA, since it is a plus-strand RNA virus and is not reverse-transcribed to DNA.
Antagonism of RIP1 using necrostatin-1 (Nec-1) ameliorated damage and inflammation of HBV X protein (HBx) in human normal hepatocytes
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Hepatitis B virus (HBV) infection is recognized as one of the major causes of chronic liver diseases, which have become a global health problem and affect millions of people worldwide [1]. HBV X protein (HBx), a protein containing 154 amino acids, is encoded by the smallest open reading frame of the DNA genome of HBV [2]. Studies have shown that HBx acts as a regulatory protein with pleiotropic effects. HBx plays an important role in enhancing HBV replication and causing various damages to hepatocytes [3]. HBx has recently been reported to induce autophagosome formation by increasing the production of reactive oxygen species (ROS) and activation of JNK [4]. Importantly, HBx causes apoptosis of hepatocytes through promoting the translocation of Bax from the cytoplasm to mitochondria, reducing mitochondrial membrane potential (MMP), and stimulating the release of cytochrome C [5]. Additionally, HBx treatment causes excessive production of several pro-inflammatory cytokines, such as interleukin-6 (IL-6), IL-8, chemokine (C-X-C motif) ligand 2 (CXCL2), and transforming growth factor-β (TGF-β), which have been considered as essential contributors to chronic liver inflammation and fibrosis [6]. Importantly, HBx could transactivate multiple intracellular signalling pathways including AP1 and NF-κB [7], which act as key regulators of inflammatory reactions in various tissue and cell types. However, the underlying molecular mechanisms are still needed to be elucidated.
Hepatitis B virus: promising drug targets and therapeutic implications
Published in Expert Opinion on Therapeutic Targets, 2021
Mohube Betty Maepa, Kristie Bloom, Abdullah Ely, Patrick Arbuthnot
Several vaccines, most of which are HBV antigen-based and administered as DNA, viral vectors or proteins, have shown therapeutic potential in animal studies. However, minimal therapeutic efficacy has been observed in humans (reviewed in [162,171]). A choice of antigen may be crucial in vaccine therapeutic efficacy. Recent studies using HBx- or HBcAg-based vaccines administered to mice carrying episomal HBV genome sequences support this notion. These studies reported HBx/HBcAg-specific CD4+ and/or CD8+ T cell responses and significant HBV DNA and/or HBV antigen loss [172,173]. Developed by GlaxoSmithKline, a vaccine based on a truncated HBcAg and full length HBsAg is in phase I clinical trial (https://clinicaltrials.gov/ct2/show/NCT03866187)
Orexin A ameliorates HBV X protein-induced cytotoxicity and inflammatory response in human hepatocytes
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Li Wang, Tao He, Baishun Wan, Xiaoqian Wang, Ling Zhang
HBV Infection of the liver may be either transient, chronic, or even lifelong, depending on the ability of the host immune response to clear the infection. Chronic infections can cause host immune-mediated liver damage, which can progress to cirrhosis and hepatocellular carcinoma. Extensive efforts have been made to prevent HBV infection-induced liver damage and host immune reactions before the disease can progress. The genome of HBV consists of four overlapped open reading frames (S, C, P and X) and expresses seven viral proteins. Among these viral proteins, HBx is one of the key determinants of viral replication and host infection. HBx is a small viral protein composed of 154 aa and can activate numerous inflammatory pathways and host-specific transcription factors [4].