Most abundant transcript (MAT) of MCMV and its multiple immunoevasion mechanisms

التفاصيل البيبلوغرافية
العنوان: Most abundant transcript (MAT) of MCMV and its multiple immunoevasion mechanisms
المؤلفون: Železnjak, Jelena, Popović, Branka, Juranić Lisnić, Vanda, L’Hernault, Anne, Lisnić, Berislav, Babić Čač, Marina, Trautwein, Nico, Halenius, Anne, Hengel, Hartmunt, Stevanović, Stefan, Krmpotić, Astrid, Dölken, Lars, Jonjić, Stipan
سنة النشر: 2016
مصطلحات موضوعية: MCMV, immunoevasion, Ly49 receptors, NK cells
الوصف: Cytomegaloviruses (CMV) have developed multiple immunoevasion strategies to compromise host’s immune response. One of the strategies involves downregulation of MHC I molecules from the cell surface to prevent T cell response. Since lack of MHC I could activate NK cells via “missing-self” mechanism, MCMV encodes for m04, a protein that binds to some MHC I molecules, escorts them to the cell surface and enables the engagement to inhibitory NK Ly49 receptors. However, some activating Ly49 receptors specifically recognize MHC I-m04 complex together with another viral component and trigger NK cells. We have narrowed down this missing factor to a novel, spliced most abundant transcript (MAT) that encompasses two viral genes, m168-m169. Furthermore, this transcript codes for at least two proteins and contains a binding site for cellular miR-27 (Juranic Lisnic et al. 2013, Marcinowski, Tanguy et al. 2012). Here we show that 5'-UTR region of MAT (uORF MAT) plays a role in the recognition of infected cells by NK through both activating and inhibitory Ly49 receptors. Our results demonstrate that uORF MAT not only affects the level of MHC I on the surface of infected cells and their maturation, but also regulates quality of peptides that are loaded onto MHC I suggesting its potential role in the evasion of T cell recognition. Furthermore, deletion of uORF MAT region of MCMV results in attenuation of the virus in vivo, affects NK cells maturation and activation and IFNγ production.
اللغة: English
URL الوصول: https://explore.openaire.eu/search/publication?articleId=57a035e5b1ae::39bba8cfa996c1dbaa93ea0ea7f139f8
https://www.bib.irb.hr/821810
Rights: CLOSED
رقم الانضمام: edsair.57a035e5b1ae..39bba8cfa996c1dbaa93ea0ea7f139f8
قاعدة البيانات: OpenAIRE