scholarly journals HBX-Mediated Migration of HBV-Replicating HepG2 Cells: Insights on Development of Hepatocellular Carcinoma

2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
Huixing Feng ◽  
Jianhua Zhang ◽  
Xi Li ◽  
Wei Ning Chen
Keyword(s):  
Cell Invasion ◽  
Rho Gtpases ◽  
Cancer Cell Invasion ◽  
Chronic Hbv Infection ◽  
Cellular Processes ◽  
Hbv Replication ◽  
Rich Domain ◽  
B Virus ◽  
Cytoskeletal Dynamics ◽  
Chronic Hbv

Hepatitus B virus (HBV) is a major cause of the development of hepatpcellular carcinoma (HCC). One of the significant characteristics of tumor progression is cell migration which is reflective of cytoskeletal dynamics. The Rho GTPases contribute to a multiple cellular processes, including the cellular cytoskeletal reorganization and motility. It has been found that some Rho GTPases have oncogenic activity and can promote cancer cell invasion. Here we discuss one of the Rho GTPases, Rac1 can be activated by HBV replication and such activation results in the high motility of HBV-replicating cells. The enhanced cell motility can be interestingly alleviated by the mutation at the sites of proline rich domain located in HBX. Our findings may provide new insights on the mechanism of HCC development associated with chronic HBV infection.

scholarly journals Multifaceted Interaction Between Hepatitis B Virus Infection and Lipid Metabolism in Hepatocytes: A Potential Target of Antiviral Therapy for Chronic Hepatitis B

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiaxuan Zhang ◽  
Ning Ling ◽  
Yu Lei ◽  
Mingli Peng ◽  
Peng Hu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Hepatic Lipid Metabolism ◽  
Chronic Hbv Infection ◽  
Hepatic Lipid ◽  
Hbv Replication ◽  
B Virus ◽  
Chronic Hbv ◽  
Related Proteins

Hepatitis B virus (HBV) is considered a “metabolic virus” and affects many hepatic metabolic pathways. However, how HBV affects lipid metabolism in hepatocytes remains uncertain yet. Accumulating clinical studies suggested that compared to non-HBV-infected controls, chronic HBV infection was associated with lower levels of serum total cholesterol and triglycerides and a lower prevalence of hepatic steatosis. In patients with chronic HBV infection, high ALT level, high body mass index, male gender, or old age was found to be positively correlated with hepatic steatosis. Furthermore, mechanisms of how HBV infection affected hepatic lipid metabolism had also been explored in a number of studies based on cell lines and mouse models. These results demonstrated that HBV replication or expression induced extensive and diverse changes in hepatic lipid metabolism, by not only activating expression of some critical lipogenesis and cholesterolgenesis-related proteins but also upregulating fatty acid oxidation and bile acid synthesis. Moreover, increasing studies found some potential targets to inhibit HBV replication or expression by decreasing or enhancing certain lipid metabolism-related proteins or metabolites. Therefore, in this article, we comprehensively reviewed these publications and revealed the connections between clinical observations and experimental findings to better understand the interaction between hepatic lipid metabolism and HBV infection. However, the available data are far from conclusive, and there is still a long way to go before clarifying the complex interaction between HBV infection and hepatic lipid metabolism.

scholarly journals Toll-Like Receptor Signaling Inhibits Hepatitis B Virus Replication In Vivo

2005 ◽  
Vol 79 (11) ◽  
pp. 7269-7272 ◽  
Author(s):  
Masanori Isogawa ◽  
Michael D. Robek ◽  
Yoshihiro Furuichi ◽  
Francis V. Chisari
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Therapeutic Strategy ◽  
Dependent Manner ◽  
Toll Like Receptor ◽  
Chronic Hbv Infection ◽  
Hbv Replication ◽  
B Virus ◽  
Chronic Hbv

ABSTRACT Toll-like receptors (TLR) play a key role in innate immunity. To examine the ability of diverse TLRs to modulate hepatitis B virus (HBV) replication, HBV transgenic mice received a single intravenous injection of ligands specific for TLR2, TLR3, TLR4, TLR5, TLR7, and TLR9. All of the ligands except for TLR2 inhibited HBV replication in the liver noncytopathically within 24 h in a α/β interferon-dependent manner. The ability of these TLR ligands to induce antiviral cytokines at the site of HBV replication suggests that TLR activation could represent a powerful and novel therapeutic strategy for the treatment of chronic HBV infection.

scholarly journals Antiviral l-Nucleosides Specific for Hepatitis B Virus Infection

2001 ◽  
Vol 45 (1) ◽  
pp. 229-235 ◽  
Author(s):  
Martin L. Bryant ◽  
Edward G. Bridges ◽  
Laurent Placidi ◽  
Abdesslem Faraj ◽  
Anna-Giulia Loi ◽  
...  
Keyword(s):  
Viral Load ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis Virus ◽  
Hbv Infection ◽  
Virus Surface ◽  
Chronic Hbv Infection ◽  
Hbv Replication ◽  
B Virus ◽  
Chronic Hbv

ABSTRACT A unique series of simple “unnatural” nucleosides has been discovered to inhibit hepatitis B virus (HBV) replication. Through structure-activity analysis it was found that the 3′-OH group of the β-l-2′-deoxyribose of the β-l-2′-deoxynucleoside confers specific antihepadnavirus activity. The unsubstituted nucleosides β-l-2′-deoxycytidine, β-l-thymidine, and β-l-2′-deoxyadenosine had the most potent, selective, and specific antiviral activity against HBV replication. Human DNA polymerases (α, β, and γ) and mitochondrial function were not affected. In the woodchuck model of chronic HBV infection, viral load was reduced by as much as 108 genome equivalents/ml of serum and there was no drug-related toxicity. In addition, the decline in woodchuck hepatitis virus surface antigen paralleled the decrease in viral load. These investigational drugs, used alone or in combination, are expected to offer new therapeutic options for patients with chronic HBV infection.

scholarly journals The Enhancer I Core Region Contributes to the Replication Level of Hepatitis B Virus In Vivo and In Vitro

2000 ◽  
Vol 74 (5) ◽  
pp. 2193-2202 ◽  
Author(s):  
C.-Thomas Bock ◽  
Nisar P. Malek ◽  
Hans L. Tillmann ◽  
Michael P. Manns ◽  
Christian Trautwein
Keyword(s):  
Liver Transplantation ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transcriptional Activity ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
Hbv Replication ◽  
B Virus ◽  
Mutant Strains ◽  
Chronic Hbv

ABSTRACT Chronic hepatitis B virus (HBV) infection can lead to liver cirrhosis and hepatocellular carcinoma. Long-term interaction of the immune system with the virus results in the selection of escape mutants and viral persistence. In this work we characterize mutations in the enhancer I region isolated prior to liver transplantation from the HBV genomes of 10 patients with chronic HBV infection. The HBV-genomes were sequenced, and the enhancer I region was cloned into luciferase reporter constructs to determine the transcriptional activity. Functional studies were performed by transfecting HBV replication-competent plasmids into hepatoma cells. Analyses of the replication fitness of the mutant strains were conducted by biochemical analysis. In all HBV genomes the enhancer I region was mutated. Most of these mutations resulted in decreased transcriptional activity. The strongest effects were detectable in strains with mutations in the hepatocyte nuclear factor 3 and 4 (HNF3 and HNF4) binding sites of the enhancer I core domain. Replication-competent HBV constructs containing these mutations demonstrated up to 10-fold-reduced levels of virus replication. Before liver transplantation, when the mutant strains were detected in the patients' sera, low HBV DNA levels were found. After transplantation and reinfection with a wild-type virus, the levels of replication were up to 240-fold higher. Our results show that mutations in the enhancer I region of HBV have a major impact on HBV replication. These mutations may also determine the switch from high to low levels of viral replication which is frequently observed during chronic HBV infection.

scholarly journals RhoBTB1 interacts with ROCKs and inhibits invasion

2019 ◽  
Vol 476 (17) ◽  
pp. 2499-2514 ◽  
Author(s):  
Raquel B. Haga ◽  
Ritu Garg ◽  
Francesca Collu ◽  
Bárbara Borda D'Agua ◽  
Sofia T. Menéndez ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cell Invasion ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Coiled Coil ◽  
Kinase Domain ◽  
Cancer Cell Invasion ◽  
Coiled Coil Region ◽  
Cytoskeletal Dynamics ◽  
Actin Cytoskeletal Dynamics

Abstract RhoBTB1 is an atypical Rho GTPase with two BTB domains in addition to its Rho domain. Although most Rho GTPases regulate actin cytoskeletal dynamics, RhoBTB1 is not known to affect cell shape or motility. We report that RhoBTB1 depletion increases prostate cancer cell invasion and induces elongation in Matrigel, a phenotype similar to that induced by depletion of ROCK1 and ROCK2. We demonstrate that RhoBTB1 associates with ROCK1 and ROCK2 and its association with ROCK1 is via its Rho domain. The Rho domain binds to the coiled-coil region of ROCK1 close to its kinase domain. We identify two amino acids within the Rho domain that alter RhoBTB1 association with ROCK1. RhoBTB1 is a substrate for ROCK1, and mutation of putative phosphorylation sites reduces its association with Cullin3, a scaffold for ubiquitin ligases. We propose that RhoBTB1 suppresses cancer cell invasion through interacting with ROCKs, which in turn regulate its association with Cullin3. Via Cullin3, RhoBTB1 has the potential to affect protein degradation.

scholarly journals Hepatitis B Virus Infection in Pregnancy: Immunological Response, Natural Course and Pregnancy Outcomes

2021 ◽  
Vol 10 (13) ◽  
pp. 2926
Author(s):  
Sirinart Sirilert ◽  
Theera Tongsong
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Pregnancy Outcomes ◽  
Natural Course ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Chronic Hbv ◽  
Adverse Pregnancy ◽  
The Impact

This review aimed to provide an update on the impact of pregnancy on the natural course of hepatitis B virus (HBV) infection and also on the impact of HBV infection on adverse pregnancy outcomes, including mother-to-child transmission (MTCT). For the literature review, original research articles, review articles, and guidelines were narratively reviewed and comprehensively validated. The databases of PubMed, EMBASE, and CINAHL were carefully searched for articles in English on topics related to HBV infection, pregnancy, and vertical transmission from 1960 to May 2021. Immunological changes during pregnancy such as suppression of Th1 response and induction of Th2 immunity lead to an impaired immune reaction to HBV and stimulate viral activity along with the reduction of CD8 T cells to escape immune detection. The impact of pregnancy on the natural course of chronic HBV infection seems to be minimal, while pregnancy can increase morbidity and mortality in the case of advanced HBV hepatitis or cirrhosis. Importantly, hepatitis flare or alanine aminotransferase (ALT) flare can occur during pregnancy and is more common during the postpartum period due to the interaction between HBV and the immune response. Interestingly, the impact of HBV infection on adverse pregnancy outcomes is more serious than ever thought. Updated evidence indicates that pregnancies with chronic HBV infection increase the risk of preterm birth and gestational diabetes, especially in cases of positive hepatitis e antigen (HBeAg).

scholarly journals G‐to‐A Hypermutation in Hepatitis B Virus (HBV) and Clinical Course of Patients with Chronic HBV Infection

2009 ◽  
Vol 199 (11) ◽  
pp. 1599-1607 ◽  
Author(s):  
Chiemi Noguchi ◽  
Michio Imamura ◽  
Masataka Tsuge ◽  
Nobuhiko Hiraga ◽  
Nami Mori ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Clinical Course ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Chronic Hbv

scholarly journals Regulation of Rho GTPases in the Vasculature by Cullin3-Based E3 Ligase Complexes

2021 ◽  
Vol 9 ◽  
Author(s):  
Fabienne Podieh ◽  
Peter L. Hordijk
Keyword(s):  
Rho Gtpases ◽  
Vascular Function ◽  
Rho Gtpase ◽  
Current Knowledge ◽  
E3 Ligase ◽  
Small Gtpases ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Ubiquitin E3 Ligase ◽  
Cytoskeletal Dynamics

Cullin3-based ubiquitin E3 ligases induce ubiquitination of substrates leading to their proteasomal or lysosomal degradation. BTB proteins serve as adaptors by binding to Cullin3 and recruiting substrate proteins, which enables specific recognition of a broad spectrum of targets. Hence, Cullin3 and its adaptors are involved in myriad cellular processes and organ functions. Cullin3-based ubiquitin E3 ligase complexes target small GTPases of the Rho subfamily, which are key regulators of cytoskeletal dynamics and cell adhesion. In this mini review, we discuss recent insights in Cullin3-mediated regulation of Rho GTPases and their impact on cellular function and disease. Intriguingly, upstream regulators of Rho GTPases are targeted by Cullin3 complexes as well. Thus, Rho GTPase signaling is regulated by Cullin3 on multiple levels. In addition, we address current knowledge of Cullin3 in regulating vascular function, focusing on its prominent role in endothelial barrier function, angiogenesis and the regulation of blood pressure.

scholarly journals The RhoA dependent anti-metastatic function of RKIP in breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gardiyawasam Kalpana ◽  
Christopher Figy ◽  
Jingwei Feng ◽  
Claire Tipton ◽  
Julius N. De Castro ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cell Invasion ◽  
Rho Gtpases ◽  
Kinase Inhibitor ◽  
Cell Movement ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis ◽  
Cytoskeleton Dynamics

AbstractRaf-1 kinase inhibitor protein was initially discovered as a physiological kinase inhibitor of the MAPK signaling pathway and was later shown to suppress cancer cell invasion and metastasis. Yet, the molecular mechanism through which RKIP executes its effects is not completely defined. RhoA has both a pro- and anti-metastatic cell-context dependent functions. Given that Rho GTPases primarily function on actin cytoskeleton dynamics and cell movement regulation, it is possible that one way RKIP hinders cancer cell invasion/metastasis is by targeting these proteins. Here we show that RKIP inhibits cancer cell invasion and metastasis by stimulating RhoA anti-tumorigenic functions. Mechanistically, RKIP activates RhoA in an Erk2 and GEF-H1 dependent manner to enhance E-cadherin membrane localization and inhibit CCL5 expression.

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