Regulation of inducible expression of syncytin-1 following influenza A/WSN/33 virus infection

Event Abstract Back to Event Regulation of inducible expression of syncytin-1 following influenza A/WSN/33 virus infection Fang Li1*, Christoffer Nellåker2, Anne-Sofie Johansson1, Björn Owe-Larsson1, Sarven Sabunciyan3 and Håkan Karlsson1* 1 Karolinska Institutet, Sweden 2 Oxford University, United Kingdom 3 Johns Hopkins School of Medicine, United States Syncytin-1, a highly fusogenic envelope protein encoded by a human endogenous retrovirus (HERV-W) element (ERVWE1 locus) on chromosome 7q21, is normally expressed exclusively in the syncytiotrophoblast layer of the human placenta. Whereas syncytin-1 appears crucially involved in the development and functioning of the human placenta, its ectopic expression in adult tissue has been associated to a range of pathological conditions, such as cancer, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), preeclampsia and schizophrenia. We previously reported on the transactivation of HERV-W elements, including that encoding syncytin-1 by influenza A/WSN/33 virus infection in a range of human cell-lines of non-placental origin. The mechanisms underlying the transactivation by virus infection were, however, not identified. qPCR analysis indicated up-regulation of transcripts encoding transcription factor glial cells missing 1 (GCM1) and syncytin-1 in response to influenza A/WSN/33 virus infection in both malignant cell-lines and primary fibroblast cells. Knock-down expression of GCM1 by siRNA, followed by viral infection suppressed the transactivation of the gene encoding syncytin-1 in CCF-STTG1 cells. Pyrosequencing analysis revealed high methylation levels of ERVWE1 promoter and enhancer regions in non-placental cells in comparison with human choriocarcinoma JEG-3 cells. No alteration of methylation status was observed between uninfected and virus infected non-placental cells. Our results indicated that inducible expression of syncytin-1 following influenza A/WSN/33 virus infection in non-placental cells come from elevation of both unspliced (corresponding to retro-viral genomes) and spliced ERVWE1 transcipts (encoding syncytin-1). Expression of syncytin-1 appear critically linked to GCM1 during both physiological and pathological conditions. Expression of the transcription factor GCM1 is required for expression of syncytin-1. References 1. Blond JL, Lavillette D, Cheynet V, Bouton O, Oriol G, Chapel-Fernandes S, Mandrand B, Mallet F, Cosset FL: An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor. J Virol 2000, 74(7):3321-3329. 2. Mi S, Lee X, Li X, Veldman GM, Finnerty H, Racie L, LaVallie E, Tang XY, Edouard P, Howes S et al: Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 2000, 403(6771):785-789. 3. Voisset C, Blancher A, Perron H, Mandrand B, Mallet F, Paranhos-Baccala G: Phylogeny of a novel family of human endogenous retrovirus sequences, HERV-W, in humans and other primates. AIDS Res Hum Retroviruses 1999, 15(17):1529-1533. 4. Lavillette D, Marin M, Ruggieri A, Mallet F, Cosset FL, Kabat D: The envelope glycoprotein of human endogenous retrovirus type W uses a divergent family of amino acid transporters/cell surface receptors. J Virol 2002, 76(13):6442-6452. 5. Bjerregaard B, Holck S, Christensen IJ, Larsson LI: Syncytin is involved in breast cancer-endothelial cell fusions. Cell Mol Life Sci 2006, 63(16):1906-1911. 6. Strick R, Ackermann S, Langbein M, Swiatek J, Schubert SW, Hashemolhosseini S, Koscheck T, Fasching PA, Schild RL, Beckmann MW et al: Proliferation and cell-cell fusion of endometrial carcinoma are induced by the human endogenous retroviral Syncytin-1 and regulated by TGF-beta. J Mol Med 2007, 85(1):23-38. 7. Antony JM, Ellestad KK, Hammond R, Imaizumi K, Mallet F, Warren KG, Power C: The human endogenous retrovirus envelope glycoprotein, syncytin-1, regulates neuroinflammation and its receptor expression in multiple sclerosis: a role for endoplasmic reticulum chaperones in astrocytes. J Immunol 2007, 179(2):1210-1224. 8. Oluwole SO, Yao Y, Conradi S, Kristensson K, Karlsson H: Elevated levels of transcripts encoding a human retroviral envelope protein (syncytin) in muscles from patients with motor neuron disease. Amyotroph Lateral Scler 2007, 8(2):67-72. 9. Perron H, Mekaoui L, Bernard C, Veas F, Stefas I, Leboyer M: Endogenous Retrovirus Type W GAG and Envelope Protein Antigenemia in Serum of Schizophrenic Patients. Biol Psychiat 2008, 64(12):1019-1023. 10. Nellaker C, Yao Y, Jones-Brando L, Mallet F, Yolken RH, Karlsson H: Transactivation of elements in the human endogenous retrovirus W family by viral infection. Retrovirology 2006, 3(1):44. 11. Cheng YH, Richardson BD, Hubert MA, Handwerger S: Isolation and characterization of the human syncytin gene promoter. Biol Reprod 2004, 70(3):694-701. 12. Prudhomme S, Oriol G, Mallet F: A retroviral promoter and a cellular enhancer define a bipartite element which controls env ERVWE1 placental expression. J Virol 2004, 78(22):12157-12168. 13. Nait-Oumesmar B, Copperman AB, Lazzarini RA: Placental expression and chromosomal localization of the human Gcm 1 gene. J Histochem Cytochem 2000, 48(7):915-922. 14. Yu C, Shen K, Lin M, Chen P, Lin C, Chang GD, Chen H: GCMa regulates the syncytin-mediated trophoblastic fusion. J Biol Chem 2002, 277(51):50062-50068. 15. Gimenez J, Montgiraud C, Oriol G, Pichon JP, Ruel K, Tsatsaris V, Gerbaud P, Frendo JL, Evain-Brion D, Mallet F: Comparative methylation of ERVWE1/syncytin-1 and other human endogenous retrovirus LTRs in placenta tissues. DNA Res 2009, 16(4):195-211. 16. Matouskova M, Blazkova J, Pajer P, Pavlicek A, Hejnar J: CpG methylation suppresses transcriptional activity of human syncytin-1 in non-placental tissues. Exp Cell Res 2006, 312(7):1011-1020. 17. Trejbalova K, Blazkova J, Matouskova M, Kucerova D, Pecnova L, Vernerova Z, Heracek J, Hirsch I, Hejnar J: Epigenetic regulation of transcription and splicing of syncytins, fusogenic glycoproteins of retroviral origin. Nucleic Acids Research 2011, 39(20):8728-8739. Keywords: human endogenous retrovirus, Syncytin-1, human placenta, transactivation, influenza A/WSN/33 virus Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: Li F, Nellåker C, Johansson A, Owe-Larsson B, Sabunciyan S and Karlsson H (2013). Regulation of inducible expression of syncytin-1 following influenza A/WSN/33 virus infection. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00440 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Fang Li, Karolinska Institutet, Stockholm, Sweden, fang.li@ki.se Dr. Håkan Karlsson, Karolinska Institutet, Stockholm, Sweden, hakkar@ki.se Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Fang Li Christoffer Nellåker Anne-Sofie Johansson Björn Owe-Larsson Sarven Sabunciyan Håkan Karlsson Google Fang Li Christoffer Nellåker Anne-Sofie Johansson Björn Owe-Larsson Sarven Sabunciyan Håkan Karlsson Google Scholar Fang Li Christoffer Nellåker Anne-Sofie Johansson Björn Owe-Larsson Sarven Sabunciyan Håkan Karlsson PubMed Fang Li Christoffer Nellåker Anne-Sofie Johansson Björn Owe-Larsson Sarven Sabunciyan Håkan Karlsson Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.