Dataset Information

Analysis of innate immune antagonism by SARS-CoV-2 reveals options for therapeutic immune modulation and differences to SARS-CoV

ABSTRACT: The novel coronavirus SARS-CoV-2 has rapidly caused a global pandemic, due to higher transmission rates and lower mortality than previous epidemic CoVs. Here, we systematically analysed changes in the proteome of HEK293 cells upon overexpression of key SARS-CoV-2 encoded proteins and compared them to changes upon SARS-CoV-2 infection.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human) Severe Acute Respiratory Syndrome Coronavirus 2

DISEASE(S): Severe Acute Respiratory Syndrome Coronavirus 2

SUBMITTER: Ignasi Forne

LAB HEAD: Prof. Dr. Axel Imhof

PROVIDER: PXD021899 | Pride | 2021-06-23

REPOSITORIES: Pride

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Publications

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

Hayn Manuel M Hirschenberger Maximilian M Koepke Lennart L Nchioua Rayhane R Straub Jan Hendrik JH Klute Susanne S Hunszinger Victoria V Zech Fabian F Prelli Bozzo Caterina C Aftab Wasim W Christensen Maria Hønholt MH Conzelmann Carina C Müller Janis Alexander JA Srinivasachar Badarinarayan Smitha S Stürzel Christina Martina CM Forne Ignasi I Stenger Steffen S Conzelmann Karl-Klaus KK Münch Jan J Schmidt Florian Ingo FI Sauter Daniel D Imhof Axel A Kirchhoff Frank F Sparrer Konstantin Maria Johannes KMJ

Cell reports 20210427 7

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 autophagos ...[more]

PMID: 33974846

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Project description:Background: Type I interferons (IFNs) are essential to the clearance of viral diseases, in part by initiating upregulation of IFN regulated genes (IRGs). A clear distinction between genes upregulated directly by virus and genes upregulated by secondary IFN production has not been made. Here we investigated the genes regulated by IFN-a2b compared to the genes regulated by SARS-CoV infection in ferrets. Methods: We characterized early host immune responses in peripheral blood and lung necropsies of ferrets injected with IFN-a2b or infected with SARS-CoV/Tor 2 strain, using microarray analysis on the Affymetrix platform. Results: We identified a common IRG signature that was upregulated in both SARS-CoV infected ferrets as well as in ferrets injected with IFN-a2b. We also identified unique patterns of gene expression for leukocyte activation, cell adhesion and complement pathways between IFN-a2b injection and SARS-CoV infection. Conclusions: Our results define the effects of IFN-a2b on the immune system of ferrets highlighting genes regulated by IFN during SARS-CoV infection. We have shown the similarities and differences of top funcional gene groups as well as pathways that play key roles in early immune responses in ferrets in response to IFN-a2b or SARS-CoV. Key words: ferret, gene expression, SARS, interferon. Keywords: time course In experiments with IFN-a2b, for peripheral blood, 15 ferrets were randomly allocated to 3 groups: Day 0, 5 ferrets (no IFN injection), day 1, 6 ferrets (injected), and day 2, 4 ferrets (injected). For lung necropsies of injected ferrets with IFN-a2b, we used 12 ferrets in 3 groups: 4 ferrets, day 0 (no IFN injection), 4 ferrets, day 1 (injected) and 4 ferrets, day 2 (injected). Experimental groups for SARS-CoV infection was as follows: For peripheral blood, 3 and 4 ferrets for day 0 (no infection) and day 2 (infection) respectively. For lung neceropsies, a total of 9 ferrets in 3 groups, each with 3 replicates for day 0 (no infection), day 1 (infection) and day 2 (infection).

Dataset Information

Analysis of innate immune antagonism by SARS-CoV-2 reveals options for therapeutic immune modulation and differences to SARS-CoV

Publications

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

Similar Datasets

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