Selected article for: "IFN receptor and iii IFN type"

Author: Hayn, Manuel; Hirschenberger, Maximilian; Koepke, Lennart; Nchioua, Rayhane; Straub, Jan Hendrik; Klute, Susanne; Hunszinger, Victoria; Zech, Fabian; Bozzo, Caterina Prelli; Aftab, Wasim; Christensen, Maria Hønholt; Conzelmann, Carina; Müller, Janis Alexander; Badarinarayan, Smitha Srinivasachar; Stürzel, Christina Martina; Forne, Ignasi; Stenger, Steffen; Conzelmann, Karl-Klaus; Münch, Jan; Schmidt, Florian Ingo; Sauter, Daniel; Imhof, Axel; Kirchhoff, Frank; Johannes Sparrer, Konstantin Maria
Title: Systematic Functional Analysis of SARS-CoV-2 Proteins Uncovers Viral Innate Immune Antagonists and Remaining Vulnerabilities
  • Cord-id: 5ymdgtir
  • Document date: 2021_4_27
  • ID: 5ymdgtir
    Snippet: SARS-CoV-2 evades most innate immune responses, but may still be vulnerable to some. Here, we systematically analyzed the impact of SARS-CoV-2 proteins on interferon (IFN) responses and autophagy. We show that SARS-CoV-2 proteins synergize to counteract antiviral immune responses. For example, Nsp14 targets the type I IFN receptor for lysosomal degradation, ORF3a prevents fusion of autophagosomes and lysosomes, and ORF7a interferes with autophagosome acidification. Most activities are evolutiona
    Document: SARS-CoV-2 evades most innate immune responses, but may still be vulnerable to some. Here, we systematically analyzed the impact of SARS-CoV-2 proteins on interferon (IFN) responses and autophagy. We show that SARS-CoV-2 proteins synergize to counteract antiviral immune responses. For example, Nsp14 targets the type I IFN receptor for lysosomal degradation, ORF3a prevents fusion of autophagosomes and lysosomes, and ORF7a interferes with autophagosome acidification. Most activities are evolutionarily conserved. However, SARS-CoV-2 Nsp15 antagonizes IFN signaling less efficiently than the orthologues of closely-related RaTG13-CoV and SARS-CoV-1. Overall, SARS-CoV-2 proteins counteract autophagy and type I IFN more efficiently than type II or III IFN signaling and infection experiments confirmed potent inhibition by IFN-γ and -λ1. Our results define the repertoire and selected mechanisms of SARS-CoV-2 innate immune antagonists, but also reveal vulnerability to type II and III IFN that may help to develop safe and effective anti-viral approaches.

    Search related documents:
    Co phrase search for related documents, hyperlinks ordered by date