CoV verursacht bei 60 Prozent auch Darmsymptome
Im Fokus des wissenschaftlichen Teams unter der Leitung von Diana Mechtcheriakova vom Institut für Pathophysiologie und Allergieforschung stand die Untersuchung von Besonderheiten und Gemeinsamkeiten in der Auswirkung von Covid-19 auf Lunge und andere Organe.
Singularity and Commonality in Response to SARS-CoV-2 in Lung and Colon
Anastasia Meshcheryakova (Institute of Pathophysiology and Allergy Research) and the Team addressed key aspects contributing to our understanding of the organ-specific manifestations of COVID-19 on the basis of comprehensive analysis of large transcriptomic datasets using a systems biology approach.
Press release was published today on MedUni NEWS and ORF NEWS.
The systemic nature of COVID-19 with multiple extrapulmonary manifestations of disease, largely due to the wide tissue expression of SARS-CoV-2 major entry factors, as well as the patient-specific features of COVID-19 pathobiology, determine important directions for basic and translational research. The compendium of aggregated clinical data reported multiple extrapulmonary manifestations of disease, including cardiovascular, hematological, renal, neurological, dermatological, and gastrointestinal manifestations. In the course of COVID-19, gastrointestinal symptoms have been reported in up to 60% of patients and may be associated with prolonged disease duration and/or poorer disease course. Understanding of organ- and tissue-specific molecular programs triggered by SARS-CoV-2 will undoubtedly contribute to the identification of novel biomarkers and treatment strategies.
The accumulated pool of transcriptomic datasets as well as the availability of powerful tools for compendium-wide analysis enables efficient extraction of novel information and knowledge gain. As an analytical solution, we developed and implemented a sophisticated analysis strategy, named by us as UNCOVIDING: Understanding COVID-19 by Integrative Data Mining. We focused on the comparison of datasets derived from transcriptomic analysis of the cellular responses triggered by SARS-CoV-2 or SARS-CoV on the basis of cellular models.
Among the major findings of this study is the uncovering of liver- and lipid metabolism-associated responses preferentially linked to the infection of the gastrointestinal system. On the contrary, the virus-triggered response in the respiratory track is strongly linked to the interferon system. This illustrates that the well-known “classical” virus-attributed molecular events were found to be characteristic for cells of lung origin.
The study additionally attracts attention to the APOBEC family and their intrinsic antiviral potential. In our previous study, we were among the first who showed tissue- and cell type-specific gene expression signatures of the individual APOBECs and emphasized the necessity to dissect the patient-specific antiviral cell state attributed to the APOBECs as a clinically relevant scenario for SARS-CoV-2 infection (Meshcheryakova et al, Front. Immunol. 2021). In continuation, we herein have brought attention to APOBEC3G as an antiviral factor being upregulated upon SARS-CoV-2 infection as part of the host defense machinery.
The study represents further implementation of systems biology-based approaches, developed in the Research Group of Diana Mechtcheriakova, aiming to dissect disease-relevant checkpoints and delineate disease pathomechanisms.
Although in the current study the authors focused on extrapulmonary manifestations in the gastrointestinal tract, the UNCOVIDING approach can be further applied to dissect the SARS-CoV-2-driven pathomechanisms in other virus-infected and -affected cell types, tissues, and organs. This is furthermore of importance in the light of newly appearing variants of SARS-CoV-2, which might trigger other symptoms by shifting the viral preference to other ACE2/TMPRSS2-positive tissues.
The results of the study have now been published as part of the Special Issue “Molecular Mechanisms of Pathogenesis, Prevention, and Therapy of COVID-19: Summarizing the Results of 2022” in the International Journal of Molecular Sciences.
This research was funded by the Medical Scientific Fund of the Mayor of the City of Vienna (Medizinisch-Wissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien)/the Foundation Fund to Promote the Fight against Tuberculosis and other Lung Diseases, Vienna, Austria (Stiftungsfond zur Förderung der Bekämpfung der Tuberkulose und anderer Lungenkrankheiten), grant number COVID043, as part of the special SARS-CoV-2/COVID-19 call.
Meshcheryakova, A.; Zimmermann, P.; Salzmann, M.; Pietschmann, P.; Mechtcheriakova, D. Singularity and Commonality in Response to SARS-CoV-2 in Lung and Colon Cell Models. Int. J. Mol. Sci. 2022, 23, 10451. doi.org/10.3390/ijms231810451
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