Molecular Virology Laboratory
Urania Georgopoulou | Department of Microbiology
Head of Laboratory
Hepatitis (B and C) is a major cause of chronic hepatitis which often leads to severe liver diseases including steatosis, cirrhosis and hepatocellular carcinoma (HCC). Moreover, ΗCV virus infects not only hepatocytes but also cells of the immune system and neuronal cells and is associated with several extrahepatic diseases.
Major advances in characterizing viral replication have led to the development of direct-acting anti-viral (DAAs) therapies that have considerably improved patient treatment outcome and can even cure chronic infection. However, a large number of challenges remain to significantly decrease HCV spread on a global scale. Indeed, 130 to 150 million people worldwide are still chronically infected with HCV (WHO), and treatments remain poorly accessible because of their high costs. Moreover, their low barrier to resistance-associated mutations combined with their inability to treat difficult patient groups, HCV-induced liver disease, and HCC all underscore the need for novel, cost-effective DAAs. Finally, a prophylactic or preventive HCV vaccine does not exist to significantly hinder HCV spread worldwide.
In the light of such complexity, studies focusing on both the host and the pathogen are required.
Our research activity is based on the study of HCV mainly focusing on its role in the establishment of chronic liver disease and liver cancer. A central aim is to elucidate the host-cell factors and pathways that are manipulated and otherwise exploited by HCV.
An additional aim is to decipher the role of T cell immune responses in order to further unravel the mechanism of HCV viral persistence. The identification of host factors that interact with viral proteins, bind to the viral genome and orchestrate essential steps in the virus life cycle can suggest targets for antiviral drugs. Furthermore, the design, production and characterization of gene delivery vehicles based on baculovirus, lentivirus and herpes virus offers promising perspectives to improve the efficacy and safety of viral-based vectors in gene therapy applications
Finally, there has also been a long-time interest in the development of viral-based vectors as delivery systems in gene therapy and vaccine development with emphasis on HSV-1 and baculovirus.
Dissecting the cellular and molecular mechanisms underlying HCV virus-host interactions
Successful completion of HCV life cycle depends on its efficient manipulation of host cell signaling and metabolic pathways. Host cell kinases play key roles in every step of the HCV life cycle. In the last decade unprecedented efforts from the pharmaceutical industry to target kinases in the context of cancer chemotherapy are in progress. Moreover, the relationship between cellular signaling and metabolism is not unidirectional. HCV utilizes host cellular lipids to assist its replication, virion assembly, secretion, trafficking and escape from host immune system. Iron is a co-morbidity factor for disease progression following HCV infection. 30–40% of chronic HCV patients have elevated serum iron, hyperferritinaemia and hepatic iron overload that correlate to poor antiviral responses. Emphasis is given on cell signalling (mediated by kinases) and metabolic (iron homeostasis and lipid metabolism) pathways altered by HCV and involved in oncogenesis and immune dysfunction.
- Delineation of MAPKs altered by HCV core protein and subviral particles
We have previously reported the generation of recombinant non-enveloped HCV core particles (HCVne) in the absence of other HCV proteins (Tsitoura P. et al., 2007, Katsarou K et al., 2010). It has previously been demonstrated that HCVne particles can efficiently enter T cells (Serti E. et al., 2010) and lead to activation of the MAPKs p38. p38 activation in T cells correlated with IL-2 transcriptional activation and was accompanied by a parallel increase of IL-2 cytokine secretion. PBMCs from healthy donors were sampled after incubation either with HCVne or the control at different time points HCVne uptake angers mainly on CD4+ T cells, which are accompanied by transcriptional activation and secretion of IL-2, IL-10, and IFN-γ over time. Our study provides strong evidence that the HCVne particles, have the potential to shape the immune response by driving T cells to partial exhaustion and finally to Treg expansion (publication: Doumba P.P., Serti E. et al., 2013).
Members involved: E. Karamichali, A. Dimitriadis, Pelagia Foka, A. Kakkanas, U.Georgpoulou (PI)
- A highly conserved YXXΦ motif in HCV core protein and HCVne
Different forms of viral particles have been identified in the serum of HCV-infected patients. HCVne can be generated by HCV core protein possessing a highly conserved ΥΧΧΦ motif and distal di-leucine motifs that confer primary endocytosis signals. In this report, we demonstrate that the YXXΦ motif of HCV core protein is crucial for the architectural integrity of HCVne because it helps them to retain their particulate form. Moreover, it could play a pivotal role in the signaling events following HCVne clathrin-mediated endocytosis by inducing the AP-2 clathrin adaptors, which in turn redirect the HCVne to the endosomal-lysosomal pathway so that it ends up co-localizing with the LDs and enhancing viral replication (publication: Karamichali E. et al., 2017).
Members involved: E. Karamichali, P. Foka, A. Kakkanas, U.Georgopoulou (PI)
- HCV and lipid metabolism. Investigate the role of ANGPTLs and LSDs
HCV relies on host lipid metabolism for its life cycle. ANGPTL-3 is a master regulator of lipid metabolism because it causes inhibition of the enzymatic activity of lipoprotein (LPL), hepatic (HL) and endothelial lipase (LIPG). In addition it is related to angiogenesis by activation of endothelial cell adhesion and migration. HCV regulates ANGPTL-3 gene transcription both in vivo and in vitro. This is the first study to report HCV core-mediated regulation of HNF-1a, albeit by a mechanism that involves loss of HNF-1a DNA binding. Promoter architecture may have played a role in this, due to sequence proximity of the two sites that may obstruct activated LXR docking on the ANGPTL-3 promoter. (P. Foka et al., 2013).
Members involved: P. Foka, (PI), V. Valliakou, G. Papdopoulou, E. Petroulia, U. Georgopoulou (PI)
- HCV mediates Iron/Hepcidin regulation (collaboration with Dr.A.Mamalaki LMBI-HPI)
Iron is crucial for life. HCV infection is associated with hepatic iron overload and elevated serum iron that correlate to poor antiviral responses. Hepcidin is a peptide hormone, a master regulator of systemic iron homeostasis and predominantly produced and secreted by hepatocytes. Because of the central role of iron metabolism, the regulation of hepcidin expression is tightly controlled in hepatocytes. HCV-mediated hepcidin regulation remains controversial. Chronic HCV patients possess relatively low hepcidin levels; however, elevated HAMP mRNA has been reported in HCV core transgenic mice and HCV replicon-expressing cells. Hepcidin regulation by core, NS5A and core naked particles of HCV are under investigation.
- A complex signalling network involving protein kinase CK2 is required for HCV core protein mediated modulation of hepcidin expression (collaboration with Dr.A.Mamalaki LMBI-HPI)
We investigated the effect of HCV core protein on HAMP gene expression and delineated the complex interplay of molecular mechanisms involved. HCV core protein up-regulated HAMP promoter activity, mRNA, and secreted protein levels. STAT3 and SMAD4 expression levels were found increased in the presence of HCV core, which orchestrated SMAD4 translocation into the nucleus and STAT3 phosphorylation. The role of the JAK/STAT activating kinase CK2 was investigated. A CK2-dominant negative construct, a CK2-specific inhibitor, and RNAi interference abrogated the core-induced increase on HAMP promoter activity, mRNA, and protein levels, while CK2 acted in synergy with core to significantly enhance HAMP gene expression (Foka et al., 2014).
Members involved: P. Foka, E. Karamichali, A. Dimitriadis, A. Kakkanas, U. Georgopoulou (PI)
- Alterations in the Iron Homeostasis Network: A Driving Force for Macrophage-mediated HCV persistency (collaboration with Dr.A.Mamalaki LMBI-HPI)
Mechanisms that favour HCV persistence over clearance are unclear, but involve defective innate immunity. We aimed to investigate interactions between HCV and hepcidin, during acute and chronic disease, and putative alterations in cellular iron homeostasis that enhance HCV propagation and promote viral persistence. HAMP expression was up-regulated early in HCV infection in vitro, with corresponding changes in ferritin and FPN. Hepcidin overexpression enhanced both viral translation and replication. In HCV-infected co-cultures, we observed increased hepcidin, reduced hepatoma ferritin and a concurrent rise in macrophaghic ferritin over time. Altered iron levels complemented amplified replication in hepatoma cells and one replication round in macrophages. Iron-loading of macrophages led to enhancement of hepatic HCV replication through reversed ferritin “flow”. Viral transmissibility from infected macrophages to naïve hepatoma cells was induced by iron. Hepcidin levels were elevated in acutely infected patients, but correlated with viral load in chronic patients. We propose that HCV control over iron occurs both by intracellular iron sequestration, through hepcidin, and intercellular iron mobilisation via ferritin, as means towards enhanced replication. Persistence could be achieved through HCV-induced changes in macrophagic iron that enhances viral replication in these cells (Foka et al., 2016. Editorial by Sikorska 2016).
Members involved: P. Foka (PI), A. Dimitriadis, E. Karamichali, U. Georgopoulou (PI)
Impact of HCV genetic variability in viral persistence
HCV has a linear positive-stranded RNA genome and displays high sequence variability caused by high mutation rates and recombination events. HCV genetic variation has been studied with regards to the virus epidemiology, response to antiviral therapy, and clinical parameters such as disease progression. Defective viral genomes lacking small or larger genomic regions are found in patients infected with HAV, HBV, HCV, HIV, dengue and influenza virus. Trans-complementation experiments in HCV showed that the blood-circulating defective genomes can be encapsidated to produce infectious particles. However, the biological role of these defective genomes in the context of natural infections is not well understood.
- Impact of defective genomes on pathogenesis of liver disease by assessment of exosomes secretion (collaboration with Dr. P. Pineau-IP, S. Benjelloun-IP Maroc F. Rouet-IP Cambodge and Dr. A. Mentis-HPI)
In order to shed light on the impact of HCV defective genomes lacking the envelope (E1/E2) region in the pathogenesis of the virus in chronic HCV patients we investigated the prevalence of the HCV natural mutants, containing large in-frame deletions (IFDMs) in the envelope region in plasma, serum and tissue biopsies of HCV-infected individuals. IFDMs were found in 20% and 8.3% of HCV needle biopsies of genotypes 1b and 2a respectively, although the latter exhibited difficulties in the amplification step. The prevalence of the IFDMs in the plasma/serum samples was 20% for genotype 2a and 26% for genotype 1b and 3a. The amplicons with the most representative deletions were cloned and the effect of the respective IFDMs in HCV replication was investigated. (E. Karamichali et al., 2016, RIIP Symposium Biomarkers).
Members involved: E. Karamichali, A. Kakkanas, U. Georgopoulou (PI)
Identify novel protein and exosomal biomarkers for early diagnosis and monitoring of HCV disease progression and response to treatment
HCC is the third most common cause of cancer mortality worldwide, and liver cirrhosis is the most important predisposing factor for it. Hepatitis B and C viral infections are the most common underlying cause of chronic liver disease. The resolution or chronicity of acute infection is dependent on a complex interplay between virus and innate/adaptive immunity. The mechanisms that lead a significant proportion of patients to more severe liver disease are not clearly defined and involve virus induced host gene/protein alterations.
- Analysis of Protein Interaction Networks for the Discovery of Hepatitis B and C Biomarkers (collaboration with Prof. K. Papaloukas and Prof. G.Thyphronitis, University of Ioannina and Prof.J. Koskinas – Faculty of Medicine, Kapodistrian University)The utilization of protein interaction networks (PINs) is expected to identify novel aspects of the disease concerning the patients’ immune response to virus, as well as the main pathways that are involved in the development of fibrosis and HCC. We designed several PINs for HBV and HCV and employed topological, modular and functional analysis techniques in order to determine significant network nodes that correspond to prominent candidate biomarkers. When PINs for HBV and HCV were compared 48 nodes were found in common, with three of them being of higher importance after statistical ranking (Simos T. et al., 2015). We are presently working to validate their classification efficacy under clinical conditions (Tsiomita S. et. al.2018).Members involved: E. Karamichali, U. Georgopoulou (PI)
- EMMPRIN modulation in HCC induced by HCV (collaboration with Dr. A. Mamalaki, LMBI-HPI).
CD147, designated as extracellular MMP inducer (EMMPRIN), is overexpressed in tumor cells. Clinical evidence showed that CD147 expression in HCC tissue is correlated with MMP-2 level and is an independent predictor of poor survival in patients with HCC. We investigated the effect of HCV on EMMPRIN gene expression.Members involved: P. Foka, A. Dimitriadis, G. Papadopoulou, U.Georgopoulou
- Investigate the role of exosomes as mediators of HCV RNA and miRNAs in the development/progression of HCC, GILEAD 2017. Coordinator: U. Georgopoulou
- Investigate the role of defective genomes in HCV infection, GILEAD 2016. Coordinator: U. Georgopoulou
- Investigate the role of exosomes as transporters of HCV viral genome, defective HCV genomes and miRNAs in liver cancer, IKY, Post-doctoral researcher: Eirini Karamichali
- The many faces of Hepatitis C virus: impact of defective genomes on pathogenesis on liver disease by assessment of exosomes secretion, ACIP 2014-2016, Institut Pasteur. Coordinator: U. Georgopoulou, Collaborators: Institut Pasteur Paris, Institut Pasteur Maroc, Institut Pasteur Cambodge
- GSRT KRHPIS – 2013ΣΕ01380025 InfeNeuTra, Institutional funding, Coordinator: E.Karagouni
- Deregulation of lipid metabolism in HCC: The HCV paradigm, EEMH 2015. Coordinators: U. Georgopoulou and Foka P. Collaborators: I. Koskinas (EKPA, Medical School)
- Recognition of New Diagnostic Biomarkers for Hepatitis Using Combined Tools from Bioinformatics and Molecular Biology (HCV-net), Operational program Epirus Thessaly Central Greece. Coordinator: K. Papaloukas (Univ. Ioannina), Collaborators: Urania Georgopoulou, G. Thyphronitis (Univ. Ioannina)
- Hepcidinanalysis: Development of automated methods for hepcidin determination and investigation of its diagnostic and pathogenetic role in diseases with deregulation of iron homeostasis, 09SYN-12-682 COOPERATION. Coordinator: A. Mamalaki, Collaborators: U. Georgopoulou (EE7 work package), G. Simos (Univ. Thessaly, E., Bairaktari (Univ. Ioannina), Medicon Hellas
- Cellular genes and proteins involved in IFN signaling after HCV, HIV and HCV/HIV infections. KEELPNO (2003 – 2005). Coordinator: U. Georgopoulou
- Bilateral Cooperation France-Greece, HCV-related HCC. GGET, 2004-2006.Coordinators: U. Georgopoulou and P. Mavromara, Collaborator: A. Epstein (Univ. Claude Bernard Lyon)
- Development of a viral system for heterologous expression and production of HCV viral like particles (VLPs) – pseudoparticles. Study of the MAPKs and NFkB signal transduction pathways by HCV VLPs.- PΕΝΕD 2003 – (1/1-2006-30/6/2009). Coordinator: U. Georgopoulou, Collaborators: G. Mosialos (Univ. Aristotle) and G. Thyphronitis (Univ. Ioannina)
USA Patent Application Title: Nucleic Acids and new polypeptides associated with and/or overlapping with HCV core products. Mavromara P., Varaklioti A., Georgopoulou U. Patent Application No: 09/644,987
ORGANIZATION OF SELECTED SCIENTIFIC MEETINGS AND WORKSHOPS
Chihab H, Jadid FZ, Foka P, Zaidane I, El Fihry R, Georgopoulou U, Marchio A, Elhabazi A, Chair M, Pineau P, Ezzikouri S, Benjelloun S. , 2018. Programmed cell death-1 3'-untranslated region polymorphism is associated with spontaneous clearance of hepatitis B virus infection. J Med Virol. 2018 Jul 17. doi: 10.1002/jmv.25265.
Molyvdas A, Georgopoulou U, Lazaridis N, Hytiroglou P, Dimitriadis A, Foka P, Vassiliadis T, Loli G, Phillipidis A, Zebekakis P, Germenis AE, Speletas M, Germanidis G., 2018, The role of the NLRP3 inflammasome and the activation of IL-1β in the pathogenesis of chronic viral hepatic inflammation., Cytokine. May 23. pii: S1043-4666(18)30185-6.
Karamitros T, Papatheodoridis G, Paraskevis D, Hatzakis A, Mbisa JL, Georgopoulou U, Klenerman P, Magiorkinis G., 2018, Impact of Interferon-α Receptor-1 Promoter Polymorphisms on the Transcriptome of the Hepatitis B Virus-Associated Hepatocellular Carcinoma. Front Immunol. Apr 16;9:777.
Karamichali, E. Serti, A. Gianneli, A. Papaefthymiou, A. Kakkanas, P. Foka, A. Seremetakis, K. Katsarou, I. P. Trougakos and U. Georgopoulou, 2017, The unexpected function of a highly conserved YXXΦ motif in HCV core protein, Infection, Genetics and Evolution 54:251-262.
E. Kaffe, A. Katsifa, N. Xylourgidis, I. Ninou, M. Zannikou, V. Harokopos, P. Foka, A. Dimitriadis, K. Evangelou, A. Moulas, U. Georgopoulou, V. Gorgoulis, G. Dalekos, V. Aidinis. 2016. Hepatocyte Autotaxin expression promotes liver fibrosis and cancer, Hepatology, Dec 16. doi: 10.1002/hep.28973. [Epub ahead of print].
Dalagiorgou G, Piperi C, Adamopoulos C, Georgopoulou U, Gargalionis AN, Spyropoulou A, Zoi I, Nokhbehsaim M, Damanaki A, Deschner J, Basdra EK, Papavassiliou AG, Cell Mol Life Sci. 2017 Mar;74(5):921-936.
Foka, P., A. Dimitriadis, E. Karamichali, E. Kyratzopoulou, D. Giannimaras, J. Koskinas, A. Varaklioti, A. Mamalaki, and U. Georgopoulou. 2016. Alterations in the iron homeostasis network: A driving force for macrophage-mediated hepatitis C virus persistency. Virulence. 7:679-90.
Karamouzis, M. V., G. Dalagiorgou, U. Georgopoulou, A. Nonni, M. Kontos, and A. G. Papavassiliou. 2016. HER-3 targeting alters the dimerization pattern of ErbB protein family members in breast carcinomas. Oncotarget 7:5576-5597.
Dalagiorgou G., Piperi C. Adamopoulos C, Georgopoulou U.,Gargalionis A.N., Spyropoulou A., Zoi I.,Nokhbehsaim M., Damanaki A.,Deschneer J., Basdra EK., Papavassiliou AG., Mechanosensor polycystin-1 potentiates differentiation of human osteoblastic cells by upregulating Runx2 expression via induction of JAK2/STAT3 signaling axis, 2016, Cellular Molecular Life Sciences, Published on line 3 October.
Doumba, P. P., E. Serti, M. Boutsikou, M. M. Konstandoulakis, U. Georgopoulou, and J. Koskinas. 2015. The role of caveolin-1 in the phenotype of human t lymphocytes after uptake of hcv non-enveloped particles. Journal of Hepatology 62:S579-S579.
Foka, P., A. Dimitriadis, E. Karamichali, E. Kyratzopoulou, D. Giannimaras, J. Koskinas, A. Mamalaki, and U. Georgopoulou. 2015. Regulation of hepcidin (hamp) as driving force for macrophage-mediated hepatitis c (hcv) persistency. Journal of Hepatology 62:S579-S580.
Simos, T., U. Georgopoulou, G. Thyphronitis, J. Koskinas, and C. Papaloukas. 2015. Analysis of Protein Interaction Networks for the Detection of Candidate Hepatitis B and C Biomarkers. Ieee Journal of Biomedical and Health Informatics 19:181-189.
Karamouzis, M; Dalagiorgou, G; Georgopoulou, U; Kontos, M; Papavassiliou, AG, Proximity ligation assay (PLA) to identify HER2-negative breast carcinomas responding in HER-3 targeting agents, 2015. Journal of clinical oncology 33 (15) Suppl: S Meeting Abstract: e22184
Foka, P., A. Dimitriadis, E. Kyratzopoulou, D. A. Giannimaras, S. Sarno, G. Simos, U. Georgopoulou, and A. Mamalaki. 2014. A complex signaling network involving protein kinase CK2 is required for hepatitis C virus core protein-mediated modulation of the iron-regulatory hepcidin gene expression. Cellular and Molecular Life Sciences 71:4243-4258.
Foka, P., E. Karamichali, G. Dalagiorgou, E. Serti, P. P. Doumba, G. Pissas, A. Kakkanas, D. Kazazi, E. Kochlios, M. Gaitanou, J. Koskinas, U. Georgopoulou, and P. Mavromara. 2014. Hepatitis C virus modulates lipid regulatory factor Angiopoietin-like 3 gene expression by repressing HNF-1 alpha activity. Journal of Hepatology 60:30-38.
Georgopoulou, U., A. Dimitriadis, P. Foka, E. Karamichali, and A. Mamalaki. 2014. Hepcidin and the iron enigma in HCV infection. Virulence 5:465-476.
Karamichali, E., P. Foka, E. Tsitoura, K. Kalliampakou, D. Kazazi, P. Karayiannis, U. Georgopoulou, and P. Mavromara. 2014. HCV NS5A co-operates with PKR in modulating HCV IRES-dependent translation. Infection Genetics and Evolution 26:113-122.
Karamouzis, M. V.; Dalagiorgou, G.; Georgopoulou, U.; et al., HER-3 targeting affects the dimerization pattern of egfr family members in breast carcinomas (BC) 2014. 39th ESMO Congress (ESMO) Annals of Oncology Volume: 25 Supplement: 4 Meeting Abstract: 176P
Dalagiorgou G, Piperi C, Georgopoulou U, Adamopoulos C, Basdra EK, Papavassiliou AG (2013). Mechanical stimulation of polycystin-1 induces human osteoblastic gene expression via potentiation of the calcineurin/NFAT signaling axis, Cell Mol Life Sci.;70(1):167-180
Doumba PP, Serti E, Boutsikou M, Konstadoulakis MM, Georgopoulou U, Koskinas J. (2013). Phenotypic and functional alterations of primary human PBMCs induced by HCV non-enveloped capsid-like particles uptake, Cell Mol Life Sci. Volume: 70, Issue: 18, Pages: 3463-3474.
Karamouzis, M.; Dalagiorgou, G.; Perez, S. A.; et al. 2013, Targeting low-expressing ERBB-2 and acquired resistant high-expressing ERBB-2 breast carcinomas, Journal of Clinical Oncology,31 (15), Supplement: S Meeting Abstract: e11513
Dalagiorgou, G; Piperi C,; Gargalionis, AN; Georgopoulou, U; Papavassiliou, AG; Basdra, EK (2012). Activation of the polycystin- calcineurin-ΝFAT axis in mechanically-stimulated osteoblastic cells, Wound Repair and Regeneration, Volume: 20, Issue: 5, Pages: A89-A89.
Foka P, E. Karamichali, P.P. Doumba, G Dalagiorgou, E. Serti, E. Kochlios, J. Koskinas, U. Georgopoulou, P. Mavromara (2012). Hepatic Nuclear Factor-1a (HNF-1a) loss of DNA binding activity is essential for HCV core –mediated modulation of lipid metabolism regulatory factor Angiopoietin –like 3 (ANGPTL3) expression Journal of Hepatology, Vol. 56Supplement 2, Page S325
E. Serti, PP Doumba, G. Thyphronitis, P. Tsitoura, K. Katsarou, P. Foka, MM Konstadoulakis, J. Koskinas, P. Mavromara, U. Georgopoulou U (2011). Modulation of IL-2 expression after uptake of hepatitis C virus non-enveloped capsid-like particles: the role of p38 kinase. Cell Mol Life Sci. 68 (3): 505-522.
Budkowska A, Kakkanas A, Nerrienet E,O Kalinina, P. Maillard, S. Viseth, Horm G. Dalagiorgou, N. Vassilaki, U. Georgopoulou, M. Martinot, A. Sall, P. Mavromara (2011). Synonymous Mutations in the Core Gene Are Linked to Unusual Serological Profile in Hepatitis C Virus Infection. PLOS ONE 6 (1): Art. No. e15871.
Boumlic A, Vassilaki N, Dalagiorgou G, E. Kochlios, A. Kakkanas, U. Georgopoulou, P. Markoulatos, G. Orfanoudakis and P. Mavromara (2011). Internal translation initiation stimulates expression of the ARF/core+1 open reading frame of HCV genotype 1b. Virus Res. 155 (1): 213-220.
Katsarou K, Tsitoura P, Georgopoulou U (2011). MEK5/ERK5/mef2: A novel signaling pathway affected by hepatitis C virus non-enveloped capsid-like particles. BBA-Molecular Cell Research 1813 (10): 1854-1862.
Doumba PP, Serti E, Boutsikou M, M.M. Konstandoulakis, U. Georgopoulou, J. Koskinas (2011). Uptake Of HCV non-enveloped particles from human peripheral blood mononuclear cells (PBMCS) leads to modulation of the immune response. Journal of Hepatology 54: S314-S314 780 Suppl. 1.
Madesis P, Osathanunkul M, Georgopoulou U, et al (2010). A hepatitis C virus core polypeptide expressed in chloroplasts detects anti-core antibodies in infected human sera. Journal of Biotechnology 145 (4): 377-386.
Katsarou K, Lavdas AA, Tsitoura P, Serti E, Markoulatos P, Mavromara, Georgopoulou U (2010). Endocytosis of hepatitis C virus non-enveloped capsid-like particles induces MAPK-ERK1/2 signaling events. Cell Mol Life Sci 67 (14): 2491-2506.
Katsarou K, Serti E, Tsitoura P, et al (2009). Green fluorescent protein - Tagged HCV non-enveloped capsid like particles: Development of a new tool for tracking HCV core uptake. Biochimie 91 (7): 903-915. Serti E., Katsarou K., Thyphronitis G., Tsitoura P., Mavromara P, Georgopoulou U (2009). Modulation of p38 signalling pathway by HCV non-enveloped capsid like particles” 34th FEBS Congress (Prague, Czech Republic, 2009). FEBS J. 276: 251 Suppl 1. Tsitoura E, Thomas J, Cuchet D, et al (2009). Infection with herpes simplex type 1-based amplicon vectors results in an IRF3/7-dependent, TLR-independent activation of the innate antiviral response in primary human fibroblasts. Journal of General Virology 90: 2209-2220 Part 9.2009
Karamichali E, Georgopoulou U, Kalliampakou K, et al (2008). The HCV, GBV-B and GBV-C effect of the non structural 5A protein on IRES-dependent translation initiation. FEBS J. 275: 406-406 Suppl. 1. Katsarou K, Serti E, Tsitoura P, et al (2008). Signaling events upon cellular uptake of recombinant HCV non-enveloped capsid-like particles. FEBS J. 275: 271-271 Suppl. 1. Nianiou I, Kalantidis K, Madesis P, et al (2008). Expression of an HCV core antigen coding gene in tobacco (N. tabacum L.). PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY 38 (4): 411-421.2008
Tsitoura P, Georgopoulou U, Petres S, et al (2007). Evidence for cellular uptake of recombinant hepatitis C virus non-enveloped capsid-like particles. FEBS LETTERS 581 (21): 4049-40572007
Post - Doctoral fellows
MSc Student EKPA