PXD026079

PXD026079 is an original dataset announced via ProteomeXchange.

Title	Differential interferon-α subtype immune signatures suppress SARS-CoV-2 infection
Description	Type I interferons (IFN-I) exert pleiotropic biological effects during viral infections, balancing virus control versus immune-mediated pathologies and have been successfully employed for the treatment of viral diseases. Humans express twelve IFN-alpha (α) subtypes, which activate downstream signalling cascades and result in distinct patterns of immune responses and differential antiviral responses. Inborn errors in type I IFN immunity and the presence of anti- IFN autoantibodies account for very severe courses of COVID-19, therefore, early administration of type I IFNs may be protective against life-threatening disease. Here we comprehensively analysed the antiviral activity of all IFNα subtypes against SARS-CoV-2 to identify the underlying immune signatures and explore their therapeutic potential. Prophylaxis of primary human airway epithelial cells (hAEC) with different IFNα subtypes during SARS-CoV-2 infection uncovered distinct functional classes with high, intermediate and low antiviral IFNs. In particular IFNα5 showed superior antiviral activity against SARS-CoV-2 infection. Dose-dependency studies further displayed additive effects upon co-administered with the broad antiviral drug remdesivir in cell culture. Transcriptomics of IFN-treated hAEC revealed different transcriptional signatures, uncovering distinct, intersecting and prototypical genes of individual IFNα subtypes. Global proteomic analyses systematically assessed the abundance of specific antiviral key effector molecules which are involved in type I IFN signalling pathways, negative regulation of viral processes and immune effector processes for the potent antiviral IFNα5. Taken together, our data provide a systemic, multi-modular definition of antiviral host responses mediated by defined type I IFNs. This knowledge shall support the development of novel therapeutic approaches against SARS-CoV-2.
HostingRepository	PRIDE
AnnounceDate	2022-02-09
AnnouncementXML	Submission_2022-06-05_14:54:54.355.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD026079
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Thilo Bracht
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-18 08:42:42	ID requested
1	2022-02-09 07:45:05	announced
⏵ 2	2022-06-05 14:54:55	announced	2022-06-05: Updated publication reference for PubMed record(s): 35131898.

Schuhenn J, Meister TL, Todt D, Bracht T, Schork K, Billaud JN, Elsner C, Heinen N, Karakoese Z, Haid S, Kumar S, Brunotte L, Eisenacher M, Di Y, Lew J, Falzarano D, Chen J, Yuan Z, Pietschmann T, Wiegmann B, Uebner H, Taube C, Le-Trilling VTK, Trilling M, Krawczyk A, Ludwig S, Sitek B, Steinmann E, Dittmer U, Lavender KJ, Sutter K, Pfaender S, subtype induced immune signatures are associated with suppression of SARS-CoV-2 infection. Proc Natl Acad Sci U S A, 119(8):(2022) [pubmed]

ProteomeXchange project tag: Sars-cov-2, Covid-19

submitter keyword: Type I IFN, IFNα subtypes, SARS-CoV-2, COVID-19, antiviral treatment, therapy, ISG

Thilo Bracht
contact affiliation	Ruhr-University Bochum Medizinisches Proteom-Center Clinical Proteomics - Translational Proteomics and University Hospital Knappschaftskrankenhaus Bochum Department of Anesthesia, Intensive Care Medicine, and Pain Therapy
contact email	thilo.bracht@rub.de
lab head
Thilo Bracht
contact affiliation	Clinical Proteomics
contact email	thilo.bracht@rub.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026079
     1. Label: PRIDE project
     2. Name: Differential interferon-α subtype immune signatures suppress SARS-CoV-2 infection