KFO309 - The clinical research unit Virus Induced Lung injury

Principal Investigators

Rory E. Morty

Dr. Rory E. Morty , PhD

JustusLiebig University Giessen
Department of Internal Medicine II
Aulweg 123; 35392 Giessen

+49-641-994-7191
Eva Friebertshäuser

Prof. Dr. rer. nat. Eva Friebertshäuser

Philipps University Marburg
Institute of Virology
Hans-Meerwein-Str. 3; 35043 Marburg

+49- 6421-2866019
Harald Ehrhardt

PD Dr. med. Harald Ehrhardt

Department of Gen. Pediatrics and Neonatology
Justus Liebig University Giessen
Feulgenstr. 12; 35392 Giessen

+49-641-985-58964

Susceptibility to viral infection driving lung injury and disruption of lung development in neonates with bronchopulmonary dysplasia

Summary

Bronchopulmonary dysplasia (BPD) is a common and serious complication of preterm birth that is associated with a pronounced stunting of the post-natal growth and impaired development of the immature lung. Patients with BPD exhibit an increased risk for respiratory syncytial virus (RSV) and influenza virus (IV) infection. Furthermore, the presence of RSV or IV as comorbidities with BPD results in increased disease severity and a worse clinical outcome, however, no study to date has explored the interactions between BPD and virus infection. 

Our previous work revealed that murine BPD is associated with substantial alterations of the inflammatory cell phenotype within the developing lung, and the impaired alveolar development correlated with recruitment of defined inflammatory cell subsets, suggesting that viral infection-associated inflammatory responses may indeed cross-talk with developmental pathways in the BDP lung to promote the disease phenotype, and vice versa, BPD lungs may be particularly permissive for viral infection due to disturbed host defense mechanisms. Using an established mouse model of BPD, we will address the following questions:
(i) Does pre-existing BPD predispose affected lungs to increased susceptibility to RSV or IV infection, leading to more severe lung injury and more pronounced respiratory failure?
(ii) Does RSV or IV infection in the background of BPD exacerbate the blunted lung development that is associated with BPD?
(iii) What mechanisms underlie the physiological interactions between virus infection and BPD?
To address these mechanisms, we will establish whether the presence of BPD creates an immunologically permissive environment for RSV and IV infection, and whether the presence of BPD modulates either the viral processing systems of the host lung, or important regulatory growth factor networks required for virus persistence. Once candidate mediators of the interaction between BPD and virus infection have been identified, we envision to draw clinical correlations in terms of mediators of BPD and virus interaction in the blood or endotracheal aspirates of infants, and also, radiological evidence of perturbations to lung development, in a cohort of preterm infants with and without BPD and confirmed viral infection.

The outcome of the proposed research will fill a key gap in our medical knowledge, furthering our understanding of how BPD influences the course of RSV and IV infection, and vice versa. These findings have the potential to substantially improve the medical management of the very high-risk group of BPD patients.

Publications

Stereological monitoring of mouse lung alveolarization from the early post-natal period to adulthood.

Am J Physiol Lung Cell Mol Physiol 2017 312(6):L882-L895. doi: 10.1152/ajplung.00492.2016

Origin and Characterization of Alpha Smooth Muscle Actin-Positive Cells During Murine Lung Development

Stem Cells 2017 35(6):1566-1578 dog:10.1002/stem.2615 Epub 2017 Apr 4




Perturbations to lysyl oxidase expression broadly influence the transcriptome of lung fibroblasts

Physiol Genomics 2017 49(8):416-429. doi: 10.1152/physiolgenomics.00026.2017




Understanding alveolarization to induce lung regeneration

Resp Res 2018 doi:10.1186/s12931-018-0837-5

Principal Investigators

Rory E. Morty

Dr. Rory E. Morty , PhD

JustusLiebig University Giessen
Department of Internal Medicine II
Aulweg 123; 35392 Giessen

+49-641-994-7191
Eva Friebertshäuser

Prof. Dr. rer. nat. Eva Friebertshäuser

Philipps University Marburg
Institute of Virology
Hans-Meerwein-Str. 3; 35043 Marburg

+49- 6421-2866019
Harald Ehrhardt

PD Dr. med. Harald Ehrhardt

Department of Gen. Pediatrics and Neonatology
Justus Liebig University Giessen
Feulgenstr. 12; 35392 Giessen

+49-641-985-58964

Project group

  • Miriam Ruth Heindl

    Miriam Ruth Heindl

    PhD student

  • David Surate

    Dr. David Surate

    Postdoc

  • Misa Gunjak

    Misa Gunjak

    PhD student

  • Ivana Mizíková

    Ivana Mizíková

    M.Sc.

  • Aybike Erdogan

    Aybike Erdogan

    Technician

  • Uta Eule

    Uta Eule

    Technician

  • Nilifer Cevik

    Nilifer Cevik

    Technician