Project Details
Projekt
AntiVir-ID: Investigating the underlying immune signatures impacting coronavirus infection
Subject Area
Virology
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 524774169
Type I interferons (IFN) exert pleiotropic biological effects during viral infections, balancing virus control versus immune-mediated pathologies. 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 course of coronavirus infection. In our previous study we comprehensively analysed the antiviral activity of all human IFNα subtypes against SARS-CoV-2 to identify the underlying immune signatures and explore their therapeutic potential. Different antiviral responses of IFNα subtypes in primary human airway epithelial cells were observed which could be separated into high, intermediate, and low antiviral activity. Global transcriptomic analysis revealed unique differentially expressed genes for each subtype, with IFNα5 expressing the largest number of unique genes. Interestingly, 42 genes were exclusively differentially regulated in the high antiviral group, including genes associated with regulation of transcription, signal transduction, and metabolic processes. In the current project we aim to elucidate the underlying immune signatures impacting coronavirus infection to understand the complex interplay between viruses and their host. First, we want to study immune effector functions controlling coronavirus infection using single and multiple ISG-KO cell lines which will be selected based on our previous study. Next, we will elucidate the temporal and spatial dynamics of IFN expression profiles and their influence on ISG signatures and immune cell activation during coronavirus infection. Further analysis of the impact of reported single nucleotide polymorphisms on IFN signaling, ISG induction and IFN-autoantibody recognition will be performed. The results of this study will further clarify the indispensable role of type I IFNs during coronavirus infection. The characterization of the IFN-mediated immune signatures controlling coronavirus will help to better understand the intricate interplay between viruses and their host for the development of novel therapeutic approaches.
DFG Programme
Research Grants
