Genetic diversity of EBV-encoded LMP1 in the Swiss HIV Cohort Study and implication for NF-Κb activation.

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State: Public
Version: Final published version
Serval ID
serval:BIB_433DE8639D2A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genetic diversity of EBV-encoded LMP1 in the Swiss HIV Cohort Study and implication for NF-Κb activation.
Journal
Plos One
Author(s)
Zuercher E., Butticaz C., Wyniger J., Martinez R., Battegay M., Boffi El Amari E., Dang T., Egger J.F., Fehr J., Mueller-Garamvögyi E., Parini A., Schaefer S.C., Schoeni-Affolter F., Thurnheer C., Tinguely M., Telenti A., Rothenberger S.
Working group(s)
Swiss HIV Cohort Study
Contributor(s)
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.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2012
Volume
7
Number
2
Pages
e32168
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
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.
Keywords
Cell Survival, Cell Transformation, Viral/genetics, DNA Mutational Analysis, Genetic Variation, HIV Infections/virology, Herpesvirus 4, Human/genetics, Humans, Lymphocytes/virology, Models, Biological, Mutation, NF-kappa B/metabolism, Phylogeny, Polymerase Chain Reaction, Polymorphism, Genetic, Viral Matrix Proteins/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
12/05/2012 9:10
Last modification date
20/08/2019 13:47
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