Details

Autor(en) / Beteiligte

• 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
• Sauter, Daniel
• Imhof, Axel
• Kirchhoff, Frank
• Sparrer, Konstantin Maria Johannes

Titel

Systematic functional analysis of SARS-CoV-2 proteins uncovers viral innate immune antagonists and remaining vulnerabilities

Ist Teil von

• Cell reports (Cambridge), 2021-05, Vol.35 (7), p.109126-109126, Article 109126

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.