ADAR1 affects HCV infection by modulating innate immune response

Maria Pujantell, Sandra Franco, Iván Galván-Femenía, Roger Badia, Marc Castellví, Edurne Garcia-Vidal, Bonaventura Clotet, Rafael de Cid, Cristina Tural, Miguel A. Martínez, Eva Riveira-Muñoz, José A. Esté, Ester Ballana

Research output: Contribution to journalArticleResearchpeer-review

9 Citations (Scopus)

Abstract

© 2018 Elsevier B.V. The hepatitis C virus (HCV) is a globally prevalent infectious pathogen. As many as 80% of people infected with HCV do not control the virus and develop a chronic infection. Response to interferon (IFN) therapy is widely variable in chronic HCV infected patients, suggesting that HCV has evolved mechanisms to suppress and evade innate immunity responsible for its control and elimination. Adenosine deaminase acting on RNA 1 (ADAR1) is a relevant factor in the regulation of the innate immune response. The loss of ADAR1 RNA-editing activity and the resulting loss of inosine bases in RNA are critical in producing aberrant RLR-mediated innate immune response, mediated by RNA sensors MDA5 and RIG-I. Here, we describe ADAR1 role as a regulator of innate and antiviral immune function in HCV infection, both in vitro and in patients. Polymorphisms within ADAR1 gene were found significantly associated to poor clinical outcome to HCV therapy and advanced liver fibrosis in a cohort of HCV and HIV-1 coinfected patients. Moreover, ADAR1 knockdown in primary macrophages and Huh7 hepatoma cells enhanced IFN and IFN stimulated gene expression and increased HCV replication in vitro. Overall, our results demonstrate that ADAR1 regulates innate immune signaling and is an important contributor to the outcome of the HCV virus–host interaction. ADAR1 is a potential target to boost antiviral immune response in HCV infection.
Original languageEnglish
Pages (from-to)116-127
JournalAntiviral Research
Volume156
DOIs
Publication statusPublished - 1 Aug 2018

Keywords

  • ADAR1
  • HCV
  • IFN
  • Innate immunity
  • RNA editing

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