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HCV was discovered and its sequence cloned in 1989, the acme of the pioneering work of Michael Houghton’s group (Choo et al., Science. 244: 359–362, 1989). Since then, studies of the HCV replication cycle have long been hampered by the following facts: (a) HCV is a strictly human pathogen that causes a chronic infection; (b) the target cells of HCV replication are solely hepatocytes; (c) virions isolated from the serum of HCV-positive patients could not infect cell culture systems in a productive manner; and (d) viral titration (assay of viral proteins and/or genome) could not be related to infectivity. Chimpanzees are permissive to HCV, but their use comes at prohibitive costs, and features of the disease are not similar to human clinical signs. Three major breakthroughs allowed to overcome these restrictions: the first one came with the discovery and implementation of the HCV replicon system in cell culture based on a full-length consensus genome from a viral RNA isolated from an infected human liver. This genome was then used to construct subgenomic replicons, which, upon transfection into a human hepatoma cell line, replicated to high levels (Lohmann et al., Science. 285: 110–113, 1999). With this invaluable tool, scientists in the field of hepatitis C were able to address fundamental questions related to viral replication in vitro, and this also fueled intensive research on antiviral molecules. The second breakthrough came with the molecular design of viral particles able to mimic the first stages of the interaction of HCV with its target cells: virion attachment to the cell surface, recognition of specific receptor molecules, internalization in intracellular compartments, and viral fusion. This tool, so-called HCV pseudoparticles (HCVpp), was based on retroviral capsids harboring the glycoproteins E1 and E2 of HCV at the virion surface. HCVpp were subsequently used to study viral entry, fusion, and humoral immune responses and to dissect the molecular details of the steps by which HCV initiated infection (Bartosch et al., J Exp Med. 197: 633–642, 2003). The third breakthrough emerged from a clinical case report in Japan of a fulminant hepatitis caused by HCV. This unusual feature for HCV led to the isolation and discovery of a new HCV clone, displaying a full replication cycle in cell culture settings. This clone was called JFH-1 (for Japanese fulminant hepatitis) and produced infectious viral particles capable of several rounds of in vitro infection, called HCVcc (HCV grown in Cell Culture) (Wakita et al., Nat Med. 11: 791–796, 2005, Lindenbach et al., Science. 309: 623–626, 2005). These particles are used for structural and functional studies and were successfully applied to the discovery of antiviral therapies now licensed and capable of HCV eradication.
Eve-Isabelle Pécheur; Fabien Zoulim; Birke Bartosch. HCV Virology. Hepatitis C: Epidemiology, Prevention and Elimination 2021, 1 -44.
AMA StyleEve-Isabelle Pécheur, Fabien Zoulim, Birke Bartosch. HCV Virology. Hepatitis C: Epidemiology, Prevention and Elimination. 2021; ():1-44.
Chicago/Turabian StyleEve-Isabelle Pécheur; Fabien Zoulim; Birke Bartosch. 2021. "HCV Virology." Hepatitis C: Epidemiology, Prevention and Elimination , no. : 1-44.
Endothelial cells exhibit distinct properties in morphology and functions in different organs that can be exploited for nanomedicine targeting. In this work, endothelial cells from different organs, i.e. brain, lung, liver, and kidney, were exposed to plain, carboxylated, and amino-modified silica. As expected, different protein coronas were formed on the different nanoparticle types and these changed when foetal bovine serum (FBS) or human serum were used. Uptake efficiencies differed strongly in the different endothelia, confirming that the cells retained some of their organ-specific differences. However, all endothelia showed higher uptake for the amino-modified silica in FBS, but, interestingly, this changed to the carboxylated silica when human serum was used, confirming that differences in the protein corona affect uptake preferences by cells. Thus, uptake rates of fluid phase markers and transferrin were determined in liver and brain endothelium to compare their endocytic activity. Overall, our results showed that endothelial cells of different organs have very different nanoparticle uptake efficiency, likely due to differences in receptor expression, affinity, and activity. A thorough characterization of phenotypic differences in the endothelia lining different organs is key to the development of targeted nanomedicine.
Aldy Aliyandi; Simon Satchell; Ronald E. Unger; Birke Bartosch; Romain Parent; Inge S. Zuhorn; Anna Salvati. Effect of endothelial cell heterogeneity on nanoparticle uptake. International Journal of Pharmaceutics 2020, 587, 119699 .
AMA StyleAldy Aliyandi, Simon Satchell, Ronald E. Unger, Birke Bartosch, Romain Parent, Inge S. Zuhorn, Anna Salvati. Effect of endothelial cell heterogeneity on nanoparticle uptake. International Journal of Pharmaceutics. 2020; 587 ():119699.
Chicago/Turabian StyleAldy Aliyandi; Simon Satchell; Ronald E. Unger; Birke Bartosch; Romain Parent; Inge S. Zuhorn; Anna Salvati. 2020. "Effect of endothelial cell heterogeneity on nanoparticle uptake." International Journal of Pharmaceutics 587, no. : 119699.
The DNA damage response (DDR) is essential to preserve genomic integrity and acts as a barrier to cancer. The ATM pathway orchestrates the cellular response to DNA double strand breaks (DSBs), and its attenuation is frequent during tumorigenesis. Here, we show that NLRP3, a Pattern Recognition Receptor known for its role in the inflammasome complex formation, interacts with the ATM kinase to control the early phase of DDR, independently of its inflammasome activity. NLRP3 down-regulation in human bronchial epithelial cells impairs ATM pathway activation as shown by an altered ATM substrate phosphorylation profile, and due to impaired p53 activation, confers resistance to acute genomic stress. Moreover, we found that NLRP3 is down-regulated in Non-Small Cell Lung Cancer (NSCLC) tissues and NLRP3 expression is correlated with patient overall survival. NLRP3 re-expression in NSCLC cells restores appropriate ATM signaling. Our findings identify a non-immune function for NLRP3 in genome integrity surveillance and strengthen the concept of a functional link between innate immunity and DNA damage sensing pathways.
Mélanie Bodnar-Wachtel; Anne-Laure Huber; Julie Gorry; Sabine Hacot; Laetitia Gerossier; Baptiste Guey; Nadège Goutagny; Birke Bartosch; Elise Ballot; Francois Ghiringhelli; Bénédicte F. Py; Yohann Couté; Annabelle Ballesta; Sylvie Lantuejoul; Janet Hall; Virginie Petrilli. NLRP3 controls ATM activation in response to DNA damage. 2020, 1 .
AMA StyleMélanie Bodnar-Wachtel, Anne-Laure Huber, Julie Gorry, Sabine Hacot, Laetitia Gerossier, Baptiste Guey, Nadège Goutagny, Birke Bartosch, Elise Ballot, Francois Ghiringhelli, Bénédicte F. Py, Yohann Couté, Annabelle Ballesta, Sylvie Lantuejoul, Janet Hall, Virginie Petrilli. NLRP3 controls ATM activation in response to DNA damage. . 2020; ():1.
Chicago/Turabian StyleMélanie Bodnar-Wachtel; Anne-Laure Huber; Julie Gorry; Sabine Hacot; Laetitia Gerossier; Baptiste Guey; Nadège Goutagny; Birke Bartosch; Elise Ballot; Francois Ghiringhelli; Bénédicte F. Py; Yohann Couté; Annabelle Ballesta; Sylvie Lantuejoul; Janet Hall; Virginie Petrilli. 2020. "NLRP3 controls ATM activation in response to DNA damage." , no. : 1.
Portal vein ligation (PVL) induces liver growth prior to resection. Associating liver partition and portal vein ligation (PVL plus transection=ALPPS) or the addition of the prolyl-hydroxylase inhibitor dimethyloxalylglycine (DMOG) to PVL both accelerate growth via stabilization of HIF-α subunits. This study aims at clarifying the crosstalk of hepatocytes (HC), hepatic stellate cells (HSC) and liver sinusoidal endothelial cells (LSEC) in accelerated liver growth. In vivo, liver volume, HC proliferation, vascular density and HSC activation were assessed in PVL, ALPPS, PVL+DMOG and DMOG alone. Proliferation of HC, HSC and LSEC was determined under DMOG in vitro. Conditioned media experiments of DMOG-exposed cells were performed. ALPPS and PVL+DMOG accelerated liver growth and HC proliferation in comparison to PVL. DMOG alone did not induce HC proliferation, but led to increased vascular density, which was also observed in ALPPS and PVL+DMOG. Activated HSC were detected in ALPPS, PVL+DMOG and DMOG, again not in PVL. In vitro, DMOG had no proliferative effect on HC, but conditioned supernatant of DMOG-treated HSC induced VEGF-dependent proliferation of LSEC. Transcriptome analysis confirmed activation of proangiogenic factors in hypoxic HSC. Hypoxia signaling in HSC induces VEGF-dependent angiogenesis. HSC play a crucial role in the cellular crosstalk of rapid liver regeneration.
Konstantin Dirscherl; Martin Schläpfer; Birgit Roth Z’Graggen; Roland H Wenger; Christa Booy; Renata Flury-Frei; Rita Fatzer; Costica Aloman; Birke Bartosch; Romain Parent; Vartan Kurtcuoglu; Diane De Zélicourt; Donat R. Spahn; Beatrice Beck Schimmer; Erik Schadde. Hypoxia sensing by hepatic stellate cells leads to VEGF-dependent angiogenesis and may contribute to accelerated liver regeneration. Scientific Reports 2020, 10, 4392 -13.
AMA StyleKonstantin Dirscherl, Martin Schläpfer, Birgit Roth Z’Graggen, Roland H Wenger, Christa Booy, Renata Flury-Frei, Rita Fatzer, Costica Aloman, Birke Bartosch, Romain Parent, Vartan Kurtcuoglu, Diane De Zélicourt, Donat R. Spahn, Beatrice Beck Schimmer, Erik Schadde. Hypoxia sensing by hepatic stellate cells leads to VEGF-dependent angiogenesis and may contribute to accelerated liver regeneration. Scientific Reports. 2020; 10 (1):4392-13.
Chicago/Turabian StyleKonstantin Dirscherl; Martin Schläpfer; Birgit Roth Z’Graggen; Roland H Wenger; Christa Booy; Renata Flury-Frei; Rita Fatzer; Costica Aloman; Birke Bartosch; Romain Parent; Vartan Kurtcuoglu; Diane De Zélicourt; Donat R. Spahn; Beatrice Beck Schimmer; Erik Schadde. 2020. "Hypoxia sensing by hepatic stellate cells leads to VEGF-dependent angiogenesis and may contribute to accelerated liver regeneration." Scientific Reports 10, no. 1: 4392-13.
Maria G. Isaguliants; Birke Bartosch; Alexander V. Ivanov. Redox Biology of Infection and Consequent Disease. Oxidative Medicine and Cellular Longevity 2020, 2020, 1 -4.
AMA StyleMaria G. Isaguliants, Birke Bartosch, Alexander V. Ivanov. Redox Biology of Infection and Consequent Disease. Oxidative Medicine and Cellular Longevity. 2020; 2020 ():1-4.
Chicago/Turabian StyleMaria G. Isaguliants; Birke Bartosch; Alexander V. Ivanov. 2020. "Redox Biology of Infection and Consequent Disease." Oxidative Medicine and Cellular Longevity 2020, no. : 1-4.
Liver fibrosis is a regenerative process that occurs after injury. It is characterized by the deposition of connective tissue by specialized fibroblasts and concomitant proliferative responses. Chronic damage that stimulates fibrogenic processes in the long-term may result in the deposition of excess matrix tissue and impairment of liver functions. End-stage fibrosis is referred to as cirrhosis and predisposes strongly to the loss of liver functions (decompensation) and hepatocellular carcinoma. Liver fibrosis is a pathology common to a number of different chronic liver diseases, including alcoholic liver disease, non-alcoholic fatty liver disease, and viral hepatitis. The predominant cell type responsible for fibrogenesis is hepatic stellate cells (HSCs). In response to inflammatory stimuli or hepatocyte death, HSCs undergo trans-differentiation to myofibroblast-like cells. Recent evidence shows that metabolic alterations in HSCs are important for the trans-differentiation process and thus offer new possibilities for therapeutic interventions. The aim of this review is to summarize current knowledge of the metabolic changes that occur during HSC activation with a particular focus on the retinol and lipid metabolism, the central carbon metabolism, and associated redox or stress-related signaling pathways.
Olga Khomich; Alexander V. Ivanov; Birke Bartosch. Metabolic Hallmarks of Hepatic Stellate Cells in Liver Fibrosis. Cells 2019, 9, 24 .
AMA StyleOlga Khomich, Alexander V. Ivanov, Birke Bartosch. Metabolic Hallmarks of Hepatic Stellate Cells in Liver Fibrosis. Cells. 2019; 9 (1):24.
Chicago/Turabian StyleOlga Khomich; Alexander V. Ivanov; Birke Bartosch. 2019. "Metabolic Hallmarks of Hepatic Stellate Cells in Liver Fibrosis." Cells 9, no. 1: 24.
It has come to our attention that the name of one of the authors was misspelt in the published version of this manuscript. Please note that ‘Birke Bartoch’ should read ‘Birke Bartosch’. In addition one of the authors, Virginie Petrilli, was not mentioned. The above author list is correct. P.V. (Virginie Petrilli) provided both reagents and supervision for flow cytometry data generation and analysis. We apologise for any inconvenience caused.
Marc Bonnin; Nadim Fares; Barbara Testoni; Yann Estornes; Kathrin Weber; Béatrice Vanbervliet; Lydie Lefrançois; Amandine Garcia; Alain Kfoury; Floriane Pez; Isabelle Coste; Pierre Saintigny; Alain Viari; Kévin Lang; Baptiste Guey; Virginie Petrilli; Valérie Hervieu; Brigitte Bancel; Birke Bartosch; David Durantel; Toufic Renno; Philippe Merle; Serge Lebecque. Corrigendum to “Toll-like receptor 3 downregulation is an escape mechanism from apoptosis during hepatocarcinogenesis” [J Hepatol 71 (2019) 763–772]. Journal of Hepatology 2019, 72, 594 .
AMA StyleMarc Bonnin, Nadim Fares, Barbara Testoni, Yann Estornes, Kathrin Weber, Béatrice Vanbervliet, Lydie Lefrançois, Amandine Garcia, Alain Kfoury, Floriane Pez, Isabelle Coste, Pierre Saintigny, Alain Viari, Kévin Lang, Baptiste Guey, Virginie Petrilli, Valérie Hervieu, Brigitte Bancel, Birke Bartosch, David Durantel, Toufic Renno, Philippe Merle, Serge Lebecque. Corrigendum to “Toll-like receptor 3 downregulation is an escape mechanism from apoptosis during hepatocarcinogenesis” [J Hepatol 71 (2019) 763–772]. Journal of Hepatology. 2019; 72 (3):594.
Chicago/Turabian StyleMarc Bonnin; Nadim Fares; Barbara Testoni; Yann Estornes; Kathrin Weber; Béatrice Vanbervliet; Lydie Lefrançois; Amandine Garcia; Alain Kfoury; Floriane Pez; Isabelle Coste; Pierre Saintigny; Alain Viari; Kévin Lang; Baptiste Guey; Virginie Petrilli; Valérie Hervieu; Brigitte Bancel; Birke Bartosch; David Durantel; Toufic Renno; Philippe Merle; Serge Lebecque. 2019. "Corrigendum to “Toll-like receptor 3 downregulation is an escape mechanism from apoptosis during hepatocarcinogenesis” [J Hepatol 71 (2019) 763–772]." Journal of Hepatology 72, no. 3: 594.
Under physiological conditions, nitric oxide (NO) produced by the endothelial NO synthase (eNOS) upregulates hepatic insulin sensitivity. Recently, contact sites between the endoplasmic reticulum and mitochondria named mitochondria-associated membranes (MAMs) emerged as a crucial hub for insulin signaling in the liver. As mitochondria are targets of NO, we explored whether NO regulates hepatic insulin sensitivity by targeting MAMs. In Huh7 cells, primary rat hepatocytes and mouse livers, enhancing NO concentration increased MAMs, whereas inhibiting eNOS decreased them. In vitro, those effects were prevented by inhibiting protein kinase G (PKG) and mimicked by activating soluble guanylate cyclase (sGC) and PKG. In agreement with the regulation of MAMs, increasing NO concentration improved insulin signaling, both in vitro and in vivo, while eNOS inhibition disrupted this response. Finally, inhibition of insulin signaling by wortmannin did not affect the impact of NO on MAMs, while experimental MAM disruption, using either targeted silencing of cyclophilin D or the overexpression of the organelle spacer fetal and adult testis-expressed 1 (FATE-1), significantly blunted the effects of NO on both MAMs and insulin response. Therefore, under physiological conditions, NO participates to the regulation of MAM integrity through the sGC/PKG pathway and concomitantly improves hepatic insulin sensitivity. Altogether, our data suggest that the induction of MAMs participate in the impact of NO on hepatocyte insulin response.
Arthur Bassot; Marie-Agnès Chauvin; Nadia Bendridi; Jingwei Ji-Cao; Guillaume Vial; Léa Monnier; Birke Bartosch; Anaïs Alves; Cécile Cottet-Rousselle; Yves Gouriou; Jennifer Rieusset; Béatrice Morio. Regulation of Mitochondria-Associated Membranes (MAMs) by NO/sGC/PKG Participates in the Control of Hepatic Insulin Response. Cells 2019, 8, 1319 .
AMA StyleArthur Bassot, Marie-Agnès Chauvin, Nadia Bendridi, Jingwei Ji-Cao, Guillaume Vial, Léa Monnier, Birke Bartosch, Anaïs Alves, Cécile Cottet-Rousselle, Yves Gouriou, Jennifer Rieusset, Béatrice Morio. Regulation of Mitochondria-Associated Membranes (MAMs) by NO/sGC/PKG Participates in the Control of Hepatic Insulin Response. Cells. 2019; 8 (11):1319.
Chicago/Turabian StyleArthur Bassot; Marie-Agnès Chauvin; Nadia Bendridi; Jingwei Ji-Cao; Guillaume Vial; Léa Monnier; Birke Bartosch; Anaïs Alves; Cécile Cottet-Rousselle; Yves Gouriou; Jennifer Rieusset; Béatrice Morio. 2019. "Regulation of Mitochondria-Associated Membranes (MAMs) by NO/sGC/PKG Participates in the Control of Hepatic Insulin Response." Cells 8, no. 11: 1319.
Hepatitis C virus (HCV) triggers massive production of reactive oxygen species (ROS) and affects expression of genes encoding ROS-scavenging enzymes. Multiple lines of evidence show that levels of ROS production contribute to the development of various virus-associated pathologies. However, investigation of HCV redox biology so far remained in the paradigm of oxidative stress, whereas no attention was given to the identification of redox switches among viral proteins. Here, we report that one of such redox switches is the NS5B protein that exhibits RNA-dependent RNA polymerase (RdRp) activity. Treatment of the recombinant protein with reducing agents significantly increases its enzymatic activity. Moreover, we show that the NS5B protein is subjected to S-glutathionylation that affects cysteine residues 89, 140, 170, 223, 274, 521, and either 279 or 295. Substitution of these cysteines except C89 and C223 with serine residues led to the reduction of the RdRp activity of the recombinant protein in a primer-dependent assay. The recombinant protein with a C279S mutation was almost inactive in vitro and could not be activated with reducing agents. In contrast, cysteine substitutions in the NS5B region in the context of a subgenomic replicon displayed opposite effects: most of the mutations enhanced HCV replication. This difference may be explained by the deleterious effect of oxidation of NS5B cysteine residues in liver cells and by the protective role of S-glutathionylation. Based on these data, redox-sensitive posttranslational modifications of HCV NS5B and other proteins merit a more detailed investigation and analysis of their role(s) in the virus life cycle and associated pathogenesis.
Marina K. Kukhanova; Vera L. Tunitskaya; Olga A. Smirnova; Olga A. Khomich; Natalia F. Zakirova; Olga N. Ivanova; Rustam Ziganshin; Birke Bartosch; Sergey N. Kochetkov; Alexander V. Ivanov. Hepatitis C Virus RNA-Dependent RNA Polymerase Is Regulated by Cysteine S-Glutathionylation. Oxidative Medicine and Cellular Longevity 2019, 2019, 1 -11.
AMA StyleMarina K. Kukhanova, Vera L. Tunitskaya, Olga A. Smirnova, Olga A. Khomich, Natalia F. Zakirova, Olga N. Ivanova, Rustam Ziganshin, Birke Bartosch, Sergey N. Kochetkov, Alexander V. Ivanov. Hepatitis C Virus RNA-Dependent RNA Polymerase Is Regulated by Cysteine S-Glutathionylation. Oxidative Medicine and Cellular Longevity. 2019; 2019 ():1-11.
Chicago/Turabian StyleMarina K. Kukhanova; Vera L. Tunitskaya; Olga A. Smirnova; Olga A. Khomich; Natalia F. Zakirova; Olga N. Ivanova; Rustam Ziganshin; Birke Bartosch; Sergey N. Kochetkov; Alexander V. Ivanov. 2019. "Hepatitis C Virus RNA-Dependent RNA Polymerase Is Regulated by Cysteine S-Glutathionylation." Oxidative Medicine and Cellular Longevity 2019, no. : 1-11.
Tumorigenesis is accompanied by the metabolic adaptation of cells to support enhanced proliferation rates and to optimize tumor persistence and amplification within the local microenvironment. In particular, cancer cells exhibit elevated levels of biogenic polyamines. Inhibitors of polyamine biosynthesis and inducers of their catabolism have been evaluated as antitumor drugs, however, their efficacy and safety remain controversial. Our goal was to investigate if drug-induced modulation of polyamine metabolism plays a role in dedifferentiation using differentiated human hepatocyte-like HepaRG cell cultures. N1,N11-diethylnorspermine (DENSpm), a potent inducer of polyamine catabolism, triggered an epithelial-mesenchymal transition (EMT)-like dedifferentiation in HepaRG cultures, as shown by down-regulation of mature hepatocytes markers and upregulation of classical EMT markers. Albeit the fact that polyamine catabolism produces H2O2, DENSpm-induced de-differentiation was not affected by antioxidants. Use of a metabolically stable spermidine analogue showed furthermore, that spermidine is a key regulator of hepatocyte differentiation. Comparative transcriptome analyses revealed, that the DENSpm-triggered dedifferentiation of HepaRG cells was accompanied by dramatic metabolic adaptations, exemplified by down-regulation of the genes of various metabolic pathways and up-regulation of the genes involved in signal transduction pathways. These results demonstrate that polyamine metabolism is tightly linked to EMT and differentiation of liver epithelial cells.
Olga N. Ivanova; Anastasiya V. Snezhkina; George S. Krasnov; Vladimir T. Valuev-Elliston; Olga A. Khomich; Alexey R. Khomutov; Tuomo A. Keinanen; Leena Alhonen; Birke Bartosch; Anna V. Kudryavtseva; Sergey N. Kochetkov; Alexander V. Ivanov. Activation of Polyamine Catabolism by N1,N11-Diethylnorspermine in Hepatic HepaRG Cells Induces Dedifferentiation and Mesenchymal-Like Phenotype. Cells 2018, 7, 275 .
AMA StyleOlga N. Ivanova, Anastasiya V. Snezhkina, George S. Krasnov, Vladimir T. Valuev-Elliston, Olga A. Khomich, Alexey R. Khomutov, Tuomo A. Keinanen, Leena Alhonen, Birke Bartosch, Anna V. Kudryavtseva, Sergey N. Kochetkov, Alexander V. Ivanov. Activation of Polyamine Catabolism by N1,N11-Diethylnorspermine in Hepatic HepaRG Cells Induces Dedifferentiation and Mesenchymal-Like Phenotype. Cells. 2018; 7 (12):275.
Chicago/Turabian StyleOlga N. Ivanova; Anastasiya V. Snezhkina; George S. Krasnov; Vladimir T. Valuev-Elliston; Olga A. Khomich; Alexey R. Khomutov; Tuomo A. Keinanen; Leena Alhonen; Birke Bartosch; Anna V. Kudryavtseva; Sergey N. Kochetkov; Alexander V. Ivanov. 2018. "Activation of Polyamine Catabolism by N1,N11-Diethylnorspermine in Hepatic HepaRG Cells Induces Dedifferentiation and Mesenchymal-Like Phenotype." Cells 7, no. 12: 275.
Respiratory viruses cause infections of the upper or lower respiratory tract and they are responsible for the common cold—the most prevalent disease in the world. In many cases the common cold results in severe illness due to complications, such as fever or pneumonia. Children, old people, and immunosuppressed patients are at the highest risk and require fast diagnosis and therapeutic intervention. However, the availability and efficiencies of existing therapeutic approaches vary depending on the virus. Investigation of the pathologies that are associated with infection by respiratory viruses will be paramount for diagnosis, treatment modalities, and the development of new therapies. Changes in redox homeostasis in infected cells are one of the key events that is linked to infection with respiratory viruses and linked to inflammation and subsequent tissue damage. Our review summarizes current knowledge on changes to redox homeostasis, as induced by the different respiratory viruses.
Olga A. Khomich; Sergey N. Kochetkov; Birke Bartosch; Alexander V. Ivanov. Redox Biology of Respiratory Viral Infections. Viruses 2018, 10, 392 .
AMA StyleOlga A. Khomich, Sergey N. Kochetkov, Birke Bartosch, Alexander V. Ivanov. Redox Biology of Respiratory Viral Infections. Viruses. 2018; 10 (8):392.
Chicago/Turabian StyleOlga A. Khomich; Sergey N. Kochetkov; Birke Bartosch; Alexander V. Ivanov. 2018. "Redox Biology of Respiratory Viral Infections." Viruses 10, no. 8: 392.
The pro‐inflammatory cytokines IL‐17 and TNFα are targets for treatment in many chronic inflammatory diseases. Here, we examined their role in liver inflammatory response compared to that of IL‐6. Human hepatoma cells (HepaRG, Huh7.5 and HepG2 cells) and primary human hepatocytes (PHH) were cultured with IL‐6, IL‐17 and/or TNFα. To determine the contribution of the IL‐6 pathway in the IL‐17/TNFα‐mediated effect, an anti‐IL‐6 receptor antibody was used. IL‐17 and TNFα increased in synergy IL‐6 secretion by HepaRG cells and PHH but not by Huh7.5 and HepG2 cells. This IL‐17/TNFα synergistic cooperation enhanced the levels of C‐reactive protein (CRP) and aspartate aminotransferase (ASAT) in HepaRG cell and PHH cultures through the induction of IL‐6. IL‐17/TNFα up‐regulated also in synergy IL‐8, MCP‐1 and CCL20 chemokines through an IL‐6‐independent pathway. Interestingly, first exposure to IL‐17, but not to TNFα, was crucial for the initiation of the IL‐17/TNFα synergistic effect on the IL‐6 and IL‐8 production. In HepaRG cells, IL‐17 enhanced the IL‐6 mRNA stability resulting in increased IL‐6 protein levels. The IL‐17A/TNFα synergistic effect on IL‐6 and IL‐8 induction was mediated through the activation of ERK‐mitogen‐activated protein kinase, nuclear factor‐κB and/or protein kinase B (Akt)–phosphatidylinositol 3‐kinase signaling pathways. Therefore, the IL‐17/TNFα synergistic interaction mediates systemic inflammation and cell damage in hepatocytes mainly through IL‐6 for CRP and ASAT induction. Independently of IL‐6, the IL‐17A/TNFα combination may also induce immune cell recruitment by chemokine up‐regulation. IL‐17 and/or TNFα neutralization can be a promising therapeutic strategy to control both systemic inflammation and liver cell attraction. This article is protected by copyright. All rights reserved.
Audrey Beringer; Ndieme Thiam; Jennifer Molle; Birke Bartosch; Pierre Miossec. Synergistic effect of interleukin-17 and tumour necrosis factor-α on inflammatory response in hepatocytes through interleukin-6-dependent and independent pathways. Clinical & Experimental Immunology 2018, 193, 221 -233.
AMA StyleAudrey Beringer, Ndieme Thiam, Jennifer Molle, Birke Bartosch, Pierre Miossec. Synergistic effect of interleukin-17 and tumour necrosis factor-α on inflammatory response in hepatocytes through interleukin-6-dependent and independent pathways. Clinical & Experimental Immunology. 2018; 193 (2):221-233.
Chicago/Turabian StyleAudrey Beringer; Ndieme Thiam; Jennifer Molle; Birke Bartosch; Pierre Miossec. 2018. "Synergistic effect of interleukin-17 and tumour necrosis factor-α on inflammatory response in hepatocytes through interleukin-6-dependent and independent pathways." Clinical & Experimental Immunology 193, no. 2: 221-233.
Reactive oxygen species (ROS) are produced in various cell compartments by an array of enzymes and processes. An excess of ROS production can be hazardous for normal cell functioning, whereas at normal levels, ROS act as vital regulators of many signal transduction pathways and transcription factors. ROS production is affected by a wide range of viruses. However, to date, the impact of viral infections has been studied only in respect to selected ROS-generating enzymes. The role of several ROS-generating and -scavenging enzymes or cellular systems in viral infections has never been addressed. In this review, we focus on the roles of biogenic polyamines and oxidative protein folding in the endoplasmic reticulum (ER) and their interplay with viruses. Polyamines act as ROS scavengers, however, their catabolism is accompanied by H2O2 production. Hydrogen peroxide is also produced during oxidative protein folding, with ER oxidoreductin 1 (Ero1) being a major source of oxidative equivalents. In addition, Ero1 controls Ca2+ efflux from the ER in response to e.g., ER stress. Here, we briefly summarize the current knowledge on the physiological roles of biogenic polyamines and the role of Ero1 at the ER, and present available data on their interplay with viral infections.
Olga A. Smirnova; Birke Bartosch; Natalia F. Zakirova; Sergey N. Kochetkov; Alexander V. Ivanov. Polyamine Metabolism and Oxidative Protein Folding in the ER as ROS-Producing Systems Neglected in Virology. International Journal of Molecular Sciences 2018, 19, 1219 .
AMA StyleOlga A. Smirnova, Birke Bartosch, Natalia F. Zakirova, Sergey N. Kochetkov, Alexander V. Ivanov. Polyamine Metabolism and Oxidative Protein Folding in the ER as ROS-Producing Systems Neglected in Virology. International Journal of Molecular Sciences. 2018; 19 (4):1219.
Chicago/Turabian StyleOlga A. Smirnova; Birke Bartosch; Natalia F. Zakirova; Sergey N. Kochetkov; Alexander V. Ivanov. 2018. "Polyamine Metabolism and Oxidative Protein Folding in the ER as ROS-Producing Systems Neglected in Virology." International Journal of Molecular Sciences 19, no. 4: 1219.
Omar M.E. Abdel-Salam; Leixuri Aguirre; Pezhman Alavi Nezhad; Fabienne T.E. Alban; Carani V. Anuradha; Sıla Appak; Juan J. Aragon; Juan Ascacio-Valdés; Rengul Cetin Atalay; Adnan Ayhancı; Robert D. Baker; Susan S. Baker; Daniela Barone; Birke Bartosch; Ruth Belmares-Cerda; Vijay K. Bharti; Birdal Bilir; Mustafa Cengiz; Denise Clavijo-Cornejo; Arul Ananth D.; Kaan Demiroren; Semra Doğru-Abbasoğlu; Irem Durmaz; Farnaz Farsi; Alfredo Fernández-Quintela; Smilin Bell Aseervatham G.; Napolitano Gaetana; Hao Gao; Hasan Gencoglu; Arup Giri; Luis E. Gomez-Quiroz; Marcela González; Mayela Govea-Salas; María C. Gutiérrez-Ruiz; Daniel Gyamfi; Hanaa A. Hassan; Weiyang He; Michal Heger; Marcus Hollenbach; Alexander V. Ivanov; Olga A. Khomich; Necla Koçak-Toker; Omer Kucuk; Asier Léniz; Rocio I.R. Macias; Jose J.G. Marin; Óscar H. Martínez-Costa; Kosha Mehta; Iñaki Milton-Laskibar; Jesus Morlett-Chávez; Nava Morshedzadeh; Enayat A. Omara; Dolores Pérez-Sala; María A. Pajares; Venditti Paola; Jinyong Peng; Maria J. Perez; Maria P. Portillo; Ana M. Rivas-Estilla; Raul Rodríguez-Herrera; KaziM Sahin; Maria A. Serrano; Nermeen M. Shaffie; Arturo Simoni-Nieves; Sarita Singhal; Rajendra S. Srivastava; Sivasudha T.; Xufeng Tao; George L. Tipoe; Müjdat Uysal; Rowan F. Van Golen; Yanfeng Wang; Jia Xiao; Noha N. Yassen; Seung K. Yoon; Rui Zhang; Lixin Zhu; Alexander Zipprich; Liangliang Zou; Alejandro Zugasti-Cruz. List of Contributors. The Liver 2018, 1 .
AMA StyleOmar M.E. Abdel-Salam, Leixuri Aguirre, Pezhman Alavi Nezhad, Fabienne T.E. Alban, Carani V. Anuradha, Sıla Appak, Juan J. Aragon, Juan Ascacio-Valdés, Rengul Cetin Atalay, Adnan Ayhancı, Robert D. Baker, Susan S. Baker, Daniela Barone, Birke Bartosch, Ruth Belmares-Cerda, Vijay K. Bharti, Birdal Bilir, Mustafa Cengiz, Denise Clavijo-Cornejo, Arul Ananth D., Kaan Demiroren, Semra Doğru-Abbasoğlu, Irem Durmaz, Farnaz Farsi, Alfredo Fernández-Quintela, Smilin Bell Aseervatham G., Napolitano Gaetana, Hao Gao, Hasan Gencoglu, Arup Giri, Luis E. Gomez-Quiroz, Marcela González, Mayela Govea-Salas, María C. Gutiérrez-Ruiz, Daniel Gyamfi, Hanaa A. Hassan, Weiyang He, Michal Heger, Marcus Hollenbach, Alexander V. Ivanov, Olga A. Khomich, Necla Koçak-Toker, Omer Kucuk, Asier Léniz, Rocio I.R. Macias, Jose J.G. Marin, Óscar H. Martínez-Costa, Kosha Mehta, Iñaki Milton-Laskibar, Jesus Morlett-Chávez, Nava Morshedzadeh, Enayat A. Omara, Dolores Pérez-Sala, María A. Pajares, Venditti Paola, Jinyong Peng, Maria J. Perez, Maria P. Portillo, Ana M. Rivas-Estilla, Raul Rodríguez-Herrera, KaziM Sahin, Maria A. Serrano, Nermeen M. Shaffie, Arturo Simoni-Nieves, Sarita Singhal, Rajendra S. Srivastava, Sivasudha T., Xufeng Tao, George L. Tipoe, Müjdat Uysal, Rowan F. Van Golen, Yanfeng Wang, Jia Xiao, Noha N. Yassen, Seung K. Yoon, Rui Zhang, Lixin Zhu, Alexander Zipprich, Liangliang Zou, Alejandro Zugasti-Cruz. List of Contributors. The Liver. 2018; ():1.
Chicago/Turabian StyleOmar M.E. Abdel-Salam; Leixuri Aguirre; Pezhman Alavi Nezhad; Fabienne T.E. Alban; Carani V. Anuradha; Sıla Appak; Juan J. Aragon; Juan Ascacio-Valdés; Rengul Cetin Atalay; Adnan Ayhancı; Robert D. Baker; Susan S. Baker; Daniela Barone; Birke Bartosch; Ruth Belmares-Cerda; Vijay K. Bharti; Birdal Bilir; Mustafa Cengiz; Denise Clavijo-Cornejo; Arul Ananth D.; Kaan Demiroren; Semra Doğru-Abbasoğlu; Irem Durmaz; Farnaz Farsi; Alfredo Fernández-Quintela; Smilin Bell Aseervatham G.; Napolitano Gaetana; Hao Gao; Hasan Gencoglu; Arup Giri; Luis E. Gomez-Quiroz; Marcela González; Mayela Govea-Salas; María C. Gutiérrez-Ruiz; Daniel Gyamfi; Hanaa A. Hassan; Weiyang He; Michal Heger; Marcus Hollenbach; Alexander V. Ivanov; Olga A. Khomich; Necla Koçak-Toker; Omer Kucuk; Asier Léniz; Rocio I.R. Macias; Jose J.G. Marin; Óscar H. Martínez-Costa; Kosha Mehta; Iñaki Milton-Laskibar; Jesus Morlett-Chávez; Nava Morshedzadeh; Enayat A. Omara; Dolores Pérez-Sala; María A. Pajares; Venditti Paola; Jinyong Peng; Maria J. Perez; Maria P. Portillo; Ana M. Rivas-Estilla; Raul Rodríguez-Herrera; KaziM Sahin; Maria A. Serrano; Nermeen M. Shaffie; Arturo Simoni-Nieves; Sarita Singhal; Rajendra S. Srivastava; Sivasudha T.; Xufeng Tao; George L. Tipoe; Müjdat Uysal; Rowan F. Van Golen; Yanfeng Wang; Jia Xiao; Noha N. Yassen; Seung K. Yoon; Rui Zhang; Lixin Zhu; Alexander Zipprich; Liangliang Zou; Alejandro Zugasti-Cruz. 2018. "List of Contributors." The Liver , no. : 1.
Chronic infection with hepatitis C virus (HCV) is characterized by liver inflammation, fibrosis, and hepatocellular carcinoma (HCC). Due to the long delay with which HCC occurs, malignant transformation is thought to be driven by indirect mechanisms. Indeed, HCV is known to create an oxidative microenvironment in the liver, which in turn stimulates repair and regeneration processes. Proliferative repair processes that occur in the context of strong oxidative stress are thought to facilitate fixation and accumulation of genetic mutations and to drive neoplastic transformation. In this review, we summarize knowledge on oxidative stress and oxidative stress responses induced by HCV. We describe the molecular mechanisms by which HCV modulates cellular systems that generate or eliminate oxidative stress and control cellular redox homeostasis. The impact of an altered cellular redox homeostasis on HCV replication, as well as the on the course and outcome of liver fibrosis and hepatocarcinogenesis are discussed.
Alexander V. Ivanov; Olga A. Khomich; Birke Bartosch. Oxidative Stress in Hepatitis C Infection. The Liver 2018, 1 -13.
AMA StyleAlexander V. Ivanov, Olga A. Khomich, Birke Bartosch. Oxidative Stress in Hepatitis C Infection. The Liver. 2018; ():1-13.
Chicago/Turabian StyleAlexander V. Ivanov; Olga A. Khomich; Birke Bartosch. 2018. "Oxidative Stress in Hepatitis C Infection." The Liver , no. : 1-13.
Olga A Smirnova; Tuomo A Keinanen; Olga N Ivanova; Mervi T Hyvonen; Sergey N Kochetkov; Birke Bartosch; Alexander V. Ivanov. Hepatitis C Virus Alters Metabolism of Biogenic Polyamines by a ROS-dependent Induction of Key Enzymes of Their Metabolism. Free Radical Biology and Medicine 2017, 112, 166 -167.
AMA StyleOlga A Smirnova, Tuomo A Keinanen, Olga N Ivanova, Mervi T Hyvonen, Sergey N Kochetkov, Birke Bartosch, Alexander V. Ivanov. Hepatitis C Virus Alters Metabolism of Biogenic Polyamines by a ROS-dependent Induction of Key Enzymes of Their Metabolism. Free Radical Biology and Medicine. 2017; 112 ():166-167.
Chicago/Turabian StyleOlga A Smirnova; Tuomo A Keinanen; Olga N Ivanova; Mervi T Hyvonen; Sergey N Kochetkov; Birke Bartosch; Alexander V. Ivanov. 2017. "Hepatitis C Virus Alters Metabolism of Biogenic Polyamines by a ROS-dependent Induction of Key Enzymes of Their Metabolism." Free Radical Biology and Medicine 112, no. : 166-167.
The roles of CD81 in the hepatitis C virus (HCV) life cycle are multiple but remain ill characterized. CD81 is known to interact with the HCV glycoproteins as an attachment factor. It also has an important role in the post-attachment entry process. Its interaction with claudin-1, for example, is vital for viral uptake and trafficking. Furthermore, CD81 and its role in membrane organization and trafficking are thought to play a pivotal role in HCV replication. Some of these functions are particularly limited to human CD81; others can be substituted with CD81 molecules from other species. However, with the exception of the large extracellular loop sequence, the structure-function analysis of CD81 in the HCV infectious cycle remains ill characterized. We describe here the fusion molecules between the large extracellular loops of human or mouse CD81 and lipid-raft-associated or unassociated GPI anchors. These fusion molecules have strong antiviral activity in a dominant negative fashion, independent of membrane raft association. Their expression in the hepatoma cell line Huh7.5 blocks HCV uptake, transmission and replication. These molecules will be useful to decipher the various roles of CD81 in the HCV life cycle and transmission in more detail.
Boyan Grigorov; Jennifer Molle; Eric Rubinstein; Fabien Zoulim; Birke Bartosch. CD81 large extracellular loop-containing fusion proteins with a dominant negative effect on HCV cell spread and replication. Journal of General Virology 2017, 98, 1646 -1657.
AMA StyleBoyan Grigorov, Jennifer Molle, Eric Rubinstein, Fabien Zoulim, Birke Bartosch. CD81 large extracellular loop-containing fusion proteins with a dominant negative effect on HCV cell spread and replication. Journal of General Virology. 2017; 98 (7):1646-1657.
Chicago/Turabian StyleBoyan Grigorov; Jennifer Molle; Eric Rubinstein; Fabien Zoulim; Birke Bartosch. 2017. "CD81 large extracellular loop-containing fusion proteins with a dominant negative effect on HCV cell spread and replication." Journal of General Virology 98, no. 7: 1646-1657.
Chronic infection with hepatitis C virus (HCV) induces liver fibrosis and cancer. In particular metabolic alterations and associated oxidative stress induced by the virus play a key role in disease progression. Albeit the pivotal role of biogenic polyamines spermine and spermidine in the regulation of liver metabolism and function and cellular control of redox homeostasis, their role in the viral life cycle has not been studied so far. Here we show that in cell lines expressing two viral proteins, capsid and the non-structural protein 5A, expression of the two key enzymes of polyamine biosynthesis and degradation, respectively, ornithine decarboxylase (ODC) and spermidine/spermine-N1-acetyl transferase (SSAT), increases transiently. In addition, both HCV core and NS5A induce sustained expression of spermine oxidase (SMO), an enzyme that catalyzes conversion of spermine into spermidine. Human hepatoma Huh7 cells harboring a full-length HCV replicon exhibited suppressed ODC and SSAT levels and elevated levels of SMO leading to decreased intracellular concentrations of spermine and spermidine. Thus, role of HCV-driven alterations of polyamine metabolism in virus replication and development of HCV-associated liver pathologies should be explored in future.
Olga A. Smirnova; Tuomo A. Keinanen; Olga N. Ivanova; Mervi T. Hyvonen; Alex R. Khomutov; Sergey Kochetkov; Birke Bartosch; Alexander V. Ivanov. Hepatitis C virus alters metabolism of biogenic polyamines by affecting expression of key enzymes of their metabolism. Biochemical and Biophysical Research Communications 2017, 483, 904 -909.
AMA StyleOlga A. Smirnova, Tuomo A. Keinanen, Olga N. Ivanova, Mervi T. Hyvonen, Alex R. Khomutov, Sergey Kochetkov, Birke Bartosch, Alexander V. Ivanov. Hepatitis C virus alters metabolism of biogenic polyamines by affecting expression of key enzymes of their metabolism. Biochemical and Biophysical Research Communications. 2017; 483 (2):904-909.
Chicago/Turabian StyleOlga A. Smirnova; Tuomo A. Keinanen; Olga N. Ivanova; Mervi T. Hyvonen; Alex R. Khomutov; Sergey Kochetkov; Birke Bartosch; Alexander V. Ivanov. 2017. "Hepatitis C virus alters metabolism of biogenic polyamines by affecting expression of key enzymes of their metabolism." Biochemical and Biophysical Research Communications 483, no. 2: 904-909.
Alexander V. Ivanov; Birke Bartosch; Maria G. Isaguliants. Oxidative Stress in Infection and Consequent Disease. Oxidative Medicine and Cellular Longevity 2017, 2017, 1 -3.
AMA StyleAlexander V. Ivanov, Birke Bartosch, Maria G. Isaguliants. Oxidative Stress in Infection and Consequent Disease. Oxidative Medicine and Cellular Longevity. 2017; 2017 ():1-3.
Chicago/Turabian StyleAlexander V. Ivanov; Birke Bartosch; Maria G. Isaguliants. 2017. "Oxidative Stress in Infection and Consequent Disease." Oxidative Medicine and Cellular Longevity 2017, no. : 1-3.
// Alexander V. Ivanov 1 , Vladimir T. Valuev-Elliston 1 , Daria A. Tyurina 1 , Olga N. Ivanova 1 , Sergey N. Kochetkov 1 , Birke Bartosch 2,3 and Maria G. Isaguliants 4,5 1 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia 2 Inserm U1052, Cancer Research Center Lyon, University of Lyon, Lyon, France 3 DevWeCan Laboratories of Excellence Network, France 4 Riga Stradins University, Riga, Latvia 5 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden Correspondence to: Alexander V. Ivanov, email: // Maria G. Isaguliants, email: // Keywords : hepatitis C virus, hepatitis B virus, reactive oxygen species, pathogenesis, carcinogenesis Received : July 22, 2016 Accepted : December 05, 2016 Published : December 11, 2016 Abstract Virally induced liver cancer usually evolves over long periods of time in the context of a strongly oxidative microenvironment, characterized by chronic liver inflammation and regeneration processes. They ultimately lead to oncogenic mutations in many cellular signaling cascades that drive cell growth and proliferation. Oxidative stress, induced by hepatitis viruses, therefore is one of the factors that drives the neoplastic transformation process in the liver. This review summarizes current knowledge on oxidative stress and oxidative stress responses induced by human hepatitis B and C viruses. It focuses on the molecular mechanisms by which these viruses activate cellular enzymes/systems that generate or scavenge reactive oxygen species (ROS) and control cellular redox homeostasis. The impact of an altered cellular redox homeostasis on the initiation and establishment of chronic viral infection, as well as on the course and outcome of liver fibrosis and hepatocarcinogenesis will be discussed The review neither discusses reactive nitrogen species, although their metabolism is interferes with that of ROS, nor antioxidants as potential therapeutic remedies against viral infections, both subjects meriting an independent review.
Alexander V. Ivanov; Vladimir T. Valuev-Elliston; Daria A. Tyurina; Olga N. Ivanova; Sergey Kochetkov; Birke Bartosch; Maria G. Isaguliants. Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis. Oncotarget 2016, 8, 3895 -3932.
AMA StyleAlexander V. Ivanov, Vladimir T. Valuev-Elliston, Daria A. Tyurina, Olga N. Ivanova, Sergey Kochetkov, Birke Bartosch, Maria G. Isaguliants. Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis. Oncotarget. 2016; 8 (3):3895-3932.
Chicago/Turabian StyleAlexander V. Ivanov; Vladimir T. Valuev-Elliston; Daria A. Tyurina; Olga N. Ivanova; Sergey Kochetkov; Birke Bartosch; Maria G. Isaguliants. 2016. "Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis." Oncotarget 8, no. 3: 3895-3932.