Aarhus University Hospital
Infectious Diseases
Trine H. Mogensen obtained her Medical degree from Aarhus University (AU) in 2002, a PhD degree in 2003, and a Doctor of Medical Sciences degree in 2009. International training includes studies in Biochemistry and in Medicine in Paris, Descartes University and Necker Medical Faculty, Research fellow in the laboratory of Professor Bryan Williams at the Cleveland Clinic, and a Diploma from the London School of Hygiene and Tropical Medicine. Since 2017 she is Professor in Infection Immunology at Department of Biomedicine, AU and holds a consultant position in the Department of Infectious diseases at Aarhus University Hospital. Her clinical work and research focus on the genetic and immunological basis of inborn errors of immunity and severe infectious diseases, most notably viral infections in the CNS. Through a translational approach combining WES of patient samples with functional studies in molecular immunology and virology, her group aims at delineating the pathogenesis of infectious diseases, including herpes simplex encephalitis, recurrent HSV-2 meningitis, VZV encephalitis, and most recently COVID-19, with the ultimate goal to improve diagnosis, prevention, and treatment of patients. Currently, she is the coordinator of the Horizon Europe-funded consortium UNDINE on human genetic and immunological determinants of the clinical manifestations of SARS-CoV-2 infection.

Moderator of 1 Session

Session Type
Parallel Sessions
Date
Thu, 13.10.2022
Session Time
10:30 - 12:00
Room
Session Hall 01

Presenter of 2 Presentations

LC3B2 and ATG4A, Autophagy and Meningitis

Session Type
Plenary Session
Date
Fri, 14.10.2022
Session Time
16:00 - 17:30
Room
Plenary Hall
Lecture Time
16:55 - 17:20

IDENTIFICATION OF HOST GENETIC VARIANTS IN THE CYTOSOLIC DNA SENSOR POL III IN PATIENTS WITH CRITICAL COVID-19

Session Type
Parallel Sessions
Date
Fri, 14.10.2022
Session Time
14:00 - 15:30
Room
Plenary Hall
Lecture Time
15:12 - 15:22

Abstract

Background and Aims

The underlying pathogenesis explaining why some individuals develop life-threatening COVID-19 disease remains incompletely understood. In this study we aim to identify gene variants predisposing specifically to vary rare cases of critical COVID-19 in young individuals without co-morbidities.

Methods

By whole exome sequencing we have identified potential disease-causing host gene variants in younger patients with critical COVID-19.

Results

We have revealed an accumulation of mutations in genes encoding the innate cytosolic DNA sensor RNA polymerase III (POL III) in younger patients with critical COVID-19. In peripheral blood mononuclear cells (PBMCs) isolated from patients with identified POL III gene variants, we have shown reduced type I interferon (IFN) responses to SARS-CoV-2 and the POL III agonist poly(dAdT). Likewise, inhibition of POL III in the pulmonary cell line A549 resulted in reduced IFN response to SARS-CoV-2. Currently, we are further scrutinizing the impact of POL III gene variants on the development of critical COVID-19 by investigating how the DNA sensor POL III is sensing infections with RNA-viruses, like SARS-CoV-2. We hypothesize that mitochondrial DNA released into the cytosol due to SARS-CoV-2-induced cellular stress during infection is sensed by POL III and mediating induction of IFN expression.

Conclusions

By regulating the IFN response to SARS-CoV-2 POL III seems to be important for prevention of development of critical COVID-19. Studies to examine the molecular mechanism, whereby host DNA may serve an antiviral role during SARS-CoV-2 infection are ongoing. Hence, this study provides new knowledge on the role of cytosolic DNA sensing and POL III in severe viral infections.

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