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Barili, Valeria; Fisicaro, Paola; Montanini, Barbara; Acerbi, Greta; Filippi, Anita; Forleo, Giovanna; Romualdi, Chiara; Ferracin, Manuela; Guerrieri, Francesca; Pedrazzi, Giuseppe; Boni, Carolina; Rossi, Marzia; Vecchi, Andrea; Penna, Amalia; Zecca, Alessandra; Mori, Cristina; Orlandini, Alessandra; Negri, Elisa; Pesci, Marco; Massari, Marco; Missale, Gabriele; Levrero, Massimo; Ottonello, Simone; Ferrari, Carlo

Targeting p53 and histone methyltransferases restores exhausted CD8+ T cells in HCV infection

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  • Medientyp: E-Artikel
  • Titel: Targeting p53 and histone methyltransferases restores exhausted CD8+ T cells in HCV infection
  • Beteiligte: Barili, Valeria; Fisicaro, Paola; Montanini, Barbara; Acerbi, Greta; Filippi, Anita; Forleo, Giovanna; Romualdi, Chiara; Ferracin, Manuela; Guerrieri, Francesca; Pedrazzi, Giuseppe; Boni, Carolina; Rossi, Marzia; Vecchi, Andrea; Penna, Amalia; Zecca, Alessandra; Mori, Cristina; Orlandini, Alessandra; Negri, Elisa; Pesci, Marco; Massari, Marco; Missale, Gabriele; Levrero, Massimo; Ottonello, Simone; Ferrari, Carlo
  • Erschienen: Springer Science and Business Media LLC, 2020
  • Erschienen in: Nature Communications, 11 (2020) 1
  • Sprache: Englisch
  • DOI: 10.1038/s41467-019-14137-7
  • ISSN: 2041-1723
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: AbstractHepatitis C virus infection (HCV) represents a unique model to characterize, from early to late stages of infection, the T cell differentiation process leading to exhaustion of human CD8+ T cells. Here we show that in early HCV infection, exhaustion-committed virus-specific CD8+ T cells display a marked upregulation of transcription associated with impaired glycolytic and mitochondrial functions, that are linked to enhanced ataxia-telangiectasia mutated (ATM) and p53 signaling. After evolution to chronic infection, exhaustion of HCV-specific T cell responses is instead characterized by a broad gene downregulation associated with a wide metabolic and anti-viral function impairment, which can be rescued by histone methyltransferase inhibitors. These results have implications not only for treatment of HCV-positive patients not responding to last-generation antivirals, but also for other chronic pathologies associated with T cell dysfunction, including cancer.
  • Zugangsstatus: Freier Zugang