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Romania, Paolo
[Author];
Cifaldi, Loredana
[Author];
Pignoloni, Benedetta
[Author];
Starc, Nadia
[Author];
D’Alicandro, Valerio
[Author];
Melaiu, Ombretta
[Author];
Li Pira, Giuseppina
[Author];
Giorda, Ezio
[Author];
Carrozzo, Rosalba
[Author];
Bergvall, Monika
[Author];
Bergström, Tomas
[Author];
Alfredsson, Lars
[Author];
Olsson, Tomas
[Author];
Kockum, Ingrid
[Author];
Seppälä, Ilkka
[Author];
Lehtimäki, Terho
[Author];
Hurme, Mikko A.
[Author];
Hengel, Hartmut
[Author];
Santoni, Angela
[Author];
Cerboni, Cristina
[Author];
Locatelli, Franco
[Author];
D’Amato, Mauro
[Author];
Fruci, Doriana
[Author]
Identification of a genetic variation in ERAP1 aminopeptidase that prevents human cytomegalovirus miR-UL112-5p-mediated immunoevasion
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- Media type: E-Book; Special Print
- Title: Identification of a genetic variation in ERAP1 aminopeptidase that prevents human cytomegalovirus miR-UL112-5p-mediated immunoevasion
- Contributor: Romania, Paolo [Author]; Cifaldi, Loredana [Author]; Pignoloni, Benedetta [Author]; Starc, Nadia [Author]; D’Alicandro, Valerio [Author]; Melaiu, Ombretta [Author]; Li Pira, Giuseppina [Author]; Giorda, Ezio [Author]; Carrozzo, Rosalba [Author]; Bergvall, Monika [Author]; Bergström, Tomas [Author]; Alfredsson, Lars [Author]; Olsson, Tomas [Author]; Kockum, Ingrid [Author]; Seppälä, Ilkka [Author]; Lehtimäki, Terho [Author]; Hurme, Mikko A. [Author]; Hengel, Hartmut [Author]; Santoni, Angela [Author]; Cerboni, Cristina [Author]; Locatelli, Franco [Author]; D’Amato, Mauro [Author]; Fruci, Doriana [Author]
-
Published:
[New York, NY]: Elsevier, 2017
- Published in: Cell reports ; 20, 4 (2017), 846-853
- Extent: 1 Online-Ressource (9 Seiten); Illustrationen, Diagramme; Supplemental Information
- Language: English
- DOI: 10.1016/j.celrep.2017.06.084
- Identifier:
- Origination:
- Footnote:
- Description: Abstract: Herein, we demonstrate that HCMV miR-UL112-5p targets ERAP1, thereby inhibiting the processing and presentation of the HCMV pp65495-503 peptide to specific CTLs. In addition, we show that the rs17481334 G variant, naturally occurring in the ERAP1 3′ UTR, preserves ERAP1 from miR-UL112-5p-mediated degradation. Specifically, HCMV miR-UL112-5p binds the 3′ UTR of ERAP1 A variant, but not the 3′ UTR of ERAP1 G variant, and, accordingly, ERAP1 expression is reduced both at RNA and protein levels only in human fibroblasts homozygous for the A variant. Consistently, HCMV-infected GG fibroblasts were more efficient in trimming viral antigens and being lysed by HCMV-peptide-specific CTLs. Notably, a significantly decreased HCMV seropositivity was detected among GG individuals suffering from multiple sclerosis, a disease model in which HCMV is negatively associated with adult-onset disorder. Overall, our results identify a resistance mechanism to HCMV miR-UL112-5p-based immune evasion strategy with potential implications for individual susceptibility to infection and other diseases
- Access State: Open Access