التفاصيل البيبلوغرافية
| العنوان: |
Systematic functional analysis of SARS-CoV-2 proteins uncovers viral innate immune antagonists and remaining vulnerabilities. |
| المؤلفون: |
Hayn, Manuel, Hirschenberger, Maximilian, Koepke, Lennart, Nchioua, Rayhane, Straub, Jan Hendrik, Klute, Susanne, Hunszinger, Victoria, Zech, Fabian, Prelli Bozzo, Caterina, Aftab, Wasim, Christensen, Maria Hønholt, Conzelmann, Carina, Müller, Janis Alexander, Srinivasachar Badarinarayan, Smitha, Stürzel, Christina Martina, Forne, Ignasi, Stenger, Steffen, Conzelmann, Karl-Klaus, Münch, Jan, Schmidt, Florian Ingo |
| المصدر: |
Cell Reports; May2021, Vol. 35 Issue 7, pN.PAG-N.PAG, 1p |
| مستخلص: |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades most innate immune responses but may still be vulnerable to some. Here, we systematically analyze the impact of SARS-CoV-2 proteins on interferon (IFN) responses and autophagy. We show that SARS-CoV-2 proteins synergize to counteract anti-viral 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 orthologs 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 confirm 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. [Display omitted] • Numerous SARS-CoV-2 proteins synergize to suppress immune sensing and signaling • Nsp14 targets IFNAR1 for lysosomal degradation • ORF3a and ORF7a block autophagy by different mechanisms • Synergistic treatment with IFN-γ and -λ1 is highly effective against SARS-CoV-2 Hayn et al. analyze the impact of individual SARS-CoV-2 proteins on virus sensing, interferon signaling, and autophagy. They define the repertoire of viral antagonists of innate immune defenses, determine selected underlying mechanisms, and identify remaining vulnerabilities of SARS-CoV-2. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
