Genetic Diversity of EBV-Encoded LMP1 in the Swiss HIV Cohort Study and Implication for NF-Κb Activation
| Autor: | Zuercher, Emilie, Butticaz, Christophe, Wyniger, Josiane, Martinez, Raquel, Battegay, Manuel, Boffi El Amari, Emmanuelle, Dang, Thanh, Egger, Jean-François, Fehr, Jan, Mueller-Garamvögyi, Esther, Parini, Andrea, Schaefer, Stephan C, Schoeni-Affolter, Franziska, Thurnheer, Christine, Tinguely, Marianne, Telenti, Amalio, Rothenberger, Sylvia, Swiss HIV Cohort Study |
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| Přispěvatelé: | Swiss HIV Cohort Study, Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., University of Zurich, Rothenberger, Sylvia |
| Rok vydání: | 2012 |
| Předmět: |
Herpesvirus 4
Human DNA Mutational Analysis lcsh:Medicine HIV Infections Polymerase Chain Reaction Hematologic Cancers and Related Disorders 10234 Clinic for Infectious Diseases 0302 clinical medicine hemic and lymphatic diseases Lymphocytes lcsh:Science Phylogeny Genetics 0303 health sciences Multidisciplinary Cancer Risk Factors NF-kappa B Transfection Phenotype 3. Good health Oncology 030220 oncology & carcinogenesis Medicine Lymphomas Research Article Cell Survival 610 Medicine & health 1100 General Agricultural and Biological Sciences Biology Models Biological Microbiology Virus Viral Matrix Proteins 03 medical and health sciences 1300 General Biochemistry Genetics and Molecular Biology Virology 10049 Institute of Pathology and Molecular Pathology otorhinolaryngologic diseases medicine Humans Transcription factor 030304 developmental biology 1000 Multidisciplinary Polymorphism Genetic Activator (genetics) lcsh:R HEK 293 cells Genetic Variation Cancers and Neoplasms Cell Transformation Viral medicine.disease Lymphoma stomatognathic diseases Nasopharyngeal carcinoma Mutation lcsh:Q Cell Transformation Viral/genetics HIV Infections/virology Herpesvirus 4 Human/genetics Lymphocytes/virology NF-kappa B/metabolism Viral Matrix Proteins/metabolism |
| Zdroj: | Zuercher, Emilie; Butticaz, Christophe; Wyniger, Josiane; Martinez, Raquel; Battegay, Manuel; Boffi El Amari, Emmanuelle; Dang, Thanh; Egger, Jean-François; Fehr, Jan; Mueller-Garamvögyi, Esther; Parini, Andrea; Schaefer, Stephan C; Schoeni-Affolter, Franziska; Thurnheer, Christine; Tinguely, Marianne; Telenti, Amalio; Rothenberger, Sylvia; Swiss HIV Cohort Study, (2012). Genetic diversity of EBV-encoded LMP1 in the Swiss HIV Cohort Study and implication for NF-Κb activation. PLoS ONE, 7(2), e32168. Lawrence, Kans.: Public Library of Science 10.1371/journal.pone.0032168 Plos One, vol. 7, no. 2, pp. e32168 PLoS ONE, Vol 7, Iss 2, p e32168 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0032168 |
| Popis: | Epstein-Barr virus (EBV) is associated with several types of cancers including Hodgkin's lymphoma (HL) and nasopharyngeal carcinoma (NPC). EBV-encoded latent membrane protein 1 (LMP1), a multifunctional oncoprotein, is a powerful activator of the transcription factor NF-κB, a property that is essential for EBV-transformed lymphoblastoid cell survival. Previous studies reported LMP1 sequence variations and induction of higher NF-κB activation levels compared to the prototype B95-8 LMP1 by some variants. Here we used biopsies of EBV-associated cancers and blood of individuals included in the Swiss HIV Cohort Study (SHCS) to analyze LMP1 genetic diversity and impact of sequence variations on LMP1-mediated NF-κB activation potential. We found that a number of variants mediate higher NF-κB activation levels when compared to B95-8 LMP1 and mapped three single polymorphisms responsible for this phenotype: F106Y, I124V and F144I. F106Y was present in all LMP1 isolated in this study and its effect was variant dependent, suggesting that it was modulated by other polymorphisms. The two polymorphisms I124V and F144I were present in distinct phylogenetic groups and were linked with other specific polymorphisms nearby, I152L and D150A/L151I, respectively. The two sets of polymorphisms, I124V/I152L and F144I/D150A/L151I, which were markers of increased NF-κB activation in vitro, were not associated with EBV-associated HL in the SHCS. Taken together these results highlighted the importance of single polymorphisms for the modulation of LMP1 signaling activity and demonstrated that several groups of LMP1 variants, through distinct mutational paths, mediated enhanced NF-κB activation levels compared to B95-8 LMP1. |
| Databáze: | OpenAIRE |
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