Nature Communications (Jan 2020)
Targeting p53 and histone methyltransferases restores exhausted CD8+ T cells in HCV infection
- Valeria Barili,
- Paola Fisicaro,
- Barbara Montanini,
- Greta Acerbi,
- Anita Filippi,
- Giovanna Forleo,
- Chiara Romualdi,
- Manuela Ferracin,
- Francesca Guerrieri,
- Giuseppe Pedrazzi,
- Carolina Boni,
- Marzia Rossi,
- Andrea Vecchi,
- Amalia Penna,
- Alessandra Zecca,
- Cristina Mori,
- Alessandra Orlandini,
- Elisa Negri,
- Marco Pesci,
- Marco Massari,
- Gabriele Missale,
- Massimo Levrero,
- Simone Ottonello,
- Carlo Ferrari
Affiliations
- Valeria Barili
- Department of Medicine and Surgery, University of Parma
- Paola Fisicaro
- Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero–Universitaria of Parma
- Barbara Montanini
- Biomolecular, Genomic and Biocomputational Sciences Unit, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma
- Greta Acerbi
- Department of Medicine and Surgery, University of Parma
- Anita Filippi
- Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero–Universitaria of Parma
- Giovanna Forleo
- Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero–Universitaria of Parma
- Chiara Romualdi
- Department of Biology, University of Padova
- Manuela Ferracin
- Department of Experimental, Diagnostic and Specialty Medicine—DIMES, University of Bologna
- Francesca Guerrieri
- Cancer Research Center of Lyon (CRCL)-INSERM U1052
- Giuseppe Pedrazzi
- Unit of Neuroscience, Department of Medicine and Surgery, Robust Statistics Academy (Ro.S.A.), University of Parma
- Carolina Boni
- Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero–Universitaria of Parma
- Marzia Rossi
- Department of Medicine and Surgery, University of Parma
- Andrea Vecchi
- Department of Medicine and Surgery, University of Parma
- Amalia Penna
- Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero–Universitaria of Parma
- Alessandra Zecca
- Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero–Universitaria of Parma
- Cristina Mori
- Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero–Universitaria of Parma
- Alessandra Orlandini
- Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero–Universitaria of Parma
- Elisa Negri
- Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero–Universitaria of Parma
- Marco Pesci
- Department of Medicine and Surgery, University of Parma
- Marco Massari
- Unit of Infectious Diseases, IRCCS–Azienda Ospedaliera S. Maria Nuova
- Gabriele Missale
- Department of Medicine and Surgery, University of Parma
- Massimo Levrero
- Cancer Research Center of Lyon (CRCL)-INSERM U1052
- Simone Ottonello
- Biomolecular, Genomic and Biocomputational Sciences Unit, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma
- Carlo Ferrari
- Department of Medicine and Surgery, University of Parma
- DOI
- https://doi.org/10.1038/s41467-019-14137-7
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 20
Abstract
Here, the authors report that exhausted HCV-specific CD8+ T cells are marked by upregulation of p53 signaling already detectable in an early phase of chronic HCV infection and by a later development of a repressive chromatin state, and show that chemical targeting of these pathways improves CD8+ T cell metabolism and antiviral function.