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

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


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


Bronchopulmonary dysplasia (BPD) is the most common and severe complication of preterm birth, characterized by stunted lung development due to oxygen support of neonates, with medically relevant consequences for respiratory health lasting into adulthood. Affected infants receiving oxygen supplementation are at risk for increased susceptibility to respiratory virus infection, namely influenza virus (IV) and respiratory syncytial virus (RSV). Furthermore, the severity of BPD is worsened when affected infants develop respiratory virus infections, either in the neonatal period; or after discharge. Despite the medically important link between preterm birth, oxygen support, and respiratory virus infections, no study to date has examined the mechanisms by which oxygen support can increase the permissiveness of the lung for viral infection, or whether the combination of lung immaturity, oxygen support, and respiratory virus infection worsens lung development in affected infants. Data generated during the first funding period of this study revealed that oxygen support increases the permissiveness of the lung for viral infections, when RSV infection was modelled in newborn mouse pups using pneumonia virus of mice (PVM). Similarly, the combination of oxygen toxicity and PVM infection in the developing lung led to worsening of lung development, compared with oxygen-injured lungs alone. In oxygen-injured lungs, tissue-resident alveolar macrophages (TR-AM) were identified to be pivotal pathogenic mediators of arrested lung development, and oxygen injury to the developing lung was documented to increase host protease activity, which may have facilitated viral replication and infection, which is thus predicted to increase viral susceptibility in developing lungs. In the second funding period, it is intended to explore the interaction between lung immaturity, viral infection, and oxygen support, at a mechanistic level; to facilitate our understanding of how a hyperoxic and a viral insult act cooperatively to drive worsening disease. Amongst the aims are to (i) identify the TR-AM subpopulation(s) that mediate(s) the impact of hyperoxia on lung development; (ii) identify the mechanisms by which oxygen toxicity drives the phenotypical transformation of lung inflammatory cells to promote viral infection, and to stunt lung development; (iii) identify which host proteases are modulated by oxygen toxicity which then creates a permissive environment for viral infection, and thus, increases the susceptibility of the oxygen-injured developing mouse lung to PVM (or IV) infection; and (iv) interrogate pharyngeal fluid harvested from BPD patients with and without respiratory virus infection, to assess whether clinical correlations may be drawn with the preclinical model, with the aim of improving medical management of affected infants to improve resistance to viral infection, and promote proper lung development, in the background of oxygen support


pH inactivation of SARS-CoV-2 and SARS-CoV in virus spiked protein A eluates from a mAb purification process

Biologicals 2024 Mar 14;86:101753. doi: 10.1016/j.biologicals.2024.101753

Sfrp1 inhibits lung fibroblast invasion during transition to injury-induced myofibroblasts

Eur Respir J 2024 Feb 8;63(2):2301326. doi: 10.1183/13993003.01326-2023

European guidelines on perinatal care: corticosteroids for women at risk of preterm birth

J Matern Fetal Neonatal Med 2023 Dec;36(1):2160628. doi: 10.1080/14767058.2022.2160628

Automated MRI Lung Segmentation and 3D Morphologic Features for Quantification of Neonatal Lung Disease

Radiol Artif Intell 2023 Oct 25;5(6):e220239. doi: 10.1148/ryai.220239

Apgar Score and Neurodevelopmental Outcomes at Age 5 Years in Infants Born Extremely Preterm

JAMA Netw Open 2023 Sep 5;6(9):e2332413. doi: 10.1001/jamanetworkopen.2023.32413

Influenza virus decreases albumin uptake and megalin expression in alveolar epithelial cells

Front Immunol 2023 Sep 1;14:1260973. doi: 10.3389/fimmu.2023.1260973

Microscopic Evidence of Malaria Infection in Visceral Tissue from Medici Family, Italy

Emerg Infect Dis 2023 Jun;29(6):1280-1283. doi: 10.3201/eid2906.230134

ERS International Congress 2022: highlights from the Paediatrics Assembly

ERJ Open Res 2023 May 22;9(3):00653-2022. doi: 10.1183/23120541.00653-2022

Expression of TMPRSS2 is up-regulated by bacterial flagellin, LPS, and Pam3Cys in human airway cells

Life Sci Alliance 2023 May 19;6(8):e202201813. doi: 10.26508/lsa.202201813

Corrigendum: Monocyte signature as a predictor of chronic lung disease in the preterm infant

Front Immunol 2023 Apr 28;14:1209992. doi: 10.3389/fimmu.2023.1209992

Monocyte signature as a predictor of chronic lung disease in the preterm infant

Front Immunol 2023 Apr 5;14:1112608. doi: 10.3389/fimmu.2023.1112608

Bacterial vesicles block viral replication in macrophages via TLR4-TRIF-axis

Cell Commun Signal 2023 Mar 28;21(1):65. doi: 10.1186/s12964-023-01086-4

TMPRSS2 Impacts Cytokine Expression in Murine Dendritic Cells

Biomedicines 2023 Feb 1;11(2):419. doi: 10.3390/biomedicines11020419

The role of influenza-A virus and coronavirus viral glycoprotein cleavage in host adaptation

Curr Opin Virol 2023 Feb;58:101303. doi: 10.1016/j.coviro.2023.101303

Evaluation of classifications of the monopodial bronchopulmonary vasculature using clustering methods

Histochem Cell Biol 2022 Nov;158(5):435-445. doi: 10.1007/s00418-022-02116-x

Improving the selectivity of 3-amidinophenylalanine-derived matriptase inhibitors

Eur J Med Chem 2022 Aug 5;238:114437. doi: 10.1016/j.ejmech.2022.114437

TMPRSS2, a novel host-directed drug target against SARS-CoV-2

Signal Transduct Target Ther 2022 Jul 23;7(1):251. doi: 10.1038/s41392-022-01084-x

TRAIL protects the immature lung from hyperoxic injury

Cell Death Dis 2022 Jul 15;13(7):614. doi: 10.1038/s41419-022-05072-5

When inflammation meets lung development-an update on the pathogenesis of bronchopulmonary dysplasia

Mol Cell Pediatr 2022 Apr 20;9(1):7. doi: 10.1186/s40348-022-00137-z

Cyclosporin A Reveals Potent Antiviral Effects in Preclinical Models of SARS-CoV-2 Infection

Am J Respir Crit Care 2022 Apr 15;205(8):964-968. doi: 10.1164/rccm.202108-1830LE

Neonatal Outcome and Treatment Perspectives of Preterm Infants at the Border of Viability

Children (Basel) 2022 Feb 24;9(3):313. doi: 10.3390/children9030313

Based Therapies to Prevent or Treat BPD-A Narrative Review on Advances and Ongoing Challenges

Int J Mol Sci 2021 Jan 24;22(3):1138. doi: 10.3390/ijms22031138

Oxygen Toxicity to the Immature Lung-Part II: The Unmet Clinical Need for Causal Therapy

Int J Mol Sci 2021 Oct 2;22(19):10694. doi: 10.3390/ijms221910694

Capillary Changes Precede Disordered Alveolarization in a Mouse Model of Bronchopulmonary Dysplasia

Am J Respir Cell Mol Biol 2021 Jul;65(1):81-91. doi: 10.1165/rcmb.2021-0004OC

WASP: a versatile, web-accessible single cell RNA-Seq processing platform

BMC Genomics 2021 Mar 18;22(1):195. doi: 10.1186/s12864-021-07469-6

Immunoglobulin deficiency as an indicator of disease severity in patients with COVID-19

Am J Physiol Lung Cell Mol Physiol 2021 Apr 1;320(4):L590-L599. doi: 10.1152/ajplung.00359.2020

Opposing Effects of TGFβ and BMP in the Pulmonary Vasculature in Congenital Diaphragmatic Hernia

Front Med (Lausanne) 2021 Mar 11;8:642577. doi: 10.3389/fmed.2021.642577

The Basicity Makes the Difference: Improved Canavanine-Derived Inhibitors of the Proprotein Convertase Furin

ACS Med Chem Lett 2021 Feb 9;12(3):426-432. doi: 10.1021/acsmedchemlett.0c00651

A comparison of airway pressures for inflation fixation of developing mouse lungs for stereological analyses

Histochem Cell Biol 2021 Feb;155(2):203-2014. doi 10.1007/s00418-020-01951-0

Immunoglobulin Deficiency as an Indicator of Disease Severity in Patients with COVID-19

Am J Physiol Lung Cell Mol 2020 Nov 25. doi 10.1152/ajplung.00359.2020

Severe organising pneumonia following COVID-19

Thorax 2020 Nov 11;thorayjnl-2020-216088. doi: 10.1136/thoraxjnl-2020-216088

Impact of litter size on survival, growth and lung alveolarization of newborn mouse pups

Ann Anat 2020 Nov;232:151579. doi: 10.1016/j.aanat.2020.151579

Minoxidil Cannot Be Used To Target Lysyl Hydroxylases during Postnatal Mouse Lung Development: A Cautionary Note

J Pharmacol Exp Ther 2020 Dec; 375(3):478-487. doi: 10.1124/jpet.120.000138

Early origins of lung disease: towards an interdisciplinary approach

Eur Respir Rev 2020 Oct 1;29(157):200191. doi: 10.1183/16000617.0191-2020

Elevated FiO2 increases SARS-CoV-2 co-receptor expression in respiratory tract epithelium

Am J Physiol Lung Cell Mol Physiol 2020 Oct 1;319(4):L670-L674. doi: 10.1152/ajplung.00345.2020

Commercially available transfection reagents and negative control siRNA are not inert

Anal Biochem 2020 Oct 1;606:113828. doi: 10.1016/j.ab.2020.113828

Correction: The genomic and clinical landscape of fetal akinesia

Genet Med 2020 Aug;22(8):1426-1428. doi: 10.1038/s41436-020-0839-9

TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells

Life Sci Alliance 2020 Jul 23;3(9):e202000786. doi: 10.26508/lsa.202000786

MSC Based Therapies-New Perspectives for the Injured Lung

J Clin Med 2020 Mar 3;9(3):682. doi: 10.3390/jcm9030682

Altered relaxation times in MRI indicate bronchopulmonary dysplasia

Thorax 2020 Feb;75(2):184-187. doi: 10.1136/thoraxjnl-2018-212384

IRE1 Signaling As a Putative Therapeutic Target in Influenza Virus-induced Pneumonia

Am J Respir Cell Mol Biol 2019 Oct;61(4):537-540. doi: 10.1165/rcmb.2019-0123LE

Ethical, Legal, and Religious Aspects at the Border of Viability

Front Pediatr 2019 May 8;7:175. doi: 10.3389/fped.2019.00175

The Tcf21 lineage constitutes the lung lipofibroblast population

Am J Physiol Lung Cell Mol Physiol 2019 May 1;316(5):L872-L885. doi: 10.1152/ajplung.00254.2018

Senescence in the lung: is this getting old?

Am J Physiol Lung Cell Mol Physiol 2019 May 1;316(5):L822-L825. doi: 10.1152/ajplung.00081.2019

Non-Invasive Ventilation in Neonatology

Dtsch Arztebl Int 2019 Mar 8;116(11):177-183. doi: 10.3238/arztebl.2019.0177

Recent advances in the pathogenesis of BPD

Semin Perinatol 2018 42(7):404-12

Recent advances in the pathogenesis of BPD

Semin Perinatol 2018 Nov;42(7):404-412. doi: 10.1053/j.semperi.2018.09.001

Understanding alveolarization to induce lung regeneration

Respir Res 2018 Aug 6;19(1):148. doi: 10.1186/s12931-018-0837-5

Activation of the NF-κB pathway alters the phenotype of MSCs in the tracheal aspirates of preterm infants with severe BPD

Am J Physiol Lung Cell Mol Physiol 2018 Jul 1;315(1):L87-L101. doi: 10.1152/ajplung.00505.2017

The Potentials and Caveats of Mesenchymal Stromal Cell-Based Therapies in the Preterm Infant

Stem Cells Int 2018 Apr 8;2018:9652897. doi: 10.1155/2018/9652897

Optimization of Substrate-Analogue Furin Inhibitors

ChemMedChem 2017 Dec 7;12(23):1953-1968. doi: 10.1002/cmdc.201700596

Red blood cell alloimmunization in neonates and children up to 3 years of age

Transfusion 2017 Nov;57(11):2720-2726. doi: 10.1111/trf.14273

Attenuated PDGF signaling drives alveolar and microvascular defects in neonatal chronic lung disease

EMBO Mol Med 2017 Nov;9(11):1504-1520. doi: 10.15252/emmm.201607308

A new target for caffeine in the developing lung: endoplasmic reticulum stress?

Am J Physiol Lung Cell Mol Physiol 2017 313(4):L659-L663

A Tale of Two Endoglins: How Does Tail-Less Soluble Endoglin Deregulate Lung Development?

Am J Respir Cell Mol Biol 2017 Oct;57(4):388-390. doi: 10.1165/rcmb.2017-0211ED

Up-date on the NeoVitaA Trial: Obstacles, challenges, perspectives, and local experiences

Wien Med Wochenschr 2017 Sep;167(11-12):264-270. doi: 10.1007/s10354-016-0500-z

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

Physiol Genomics 2017 Aug 1;49(8):416-429. doi: 10.1152/physiolgenomics.00026.2017

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

Am J Physiol Lung Cell Mol Physiol 2017 Jun 1;312(6):L882-L895. doi: 10.1152/ajplung.00492.2016

Two-Way Conversion between Lipogenic and Myogenic Fibroblastic Phenotypes Marks the Progression and Resolution of Lung Fibrosis

Cell Stem Cell 2017 Feb 2;20(2):261-273.e3. doi: 10.1016/j.stem.2016.10.004. Epub 2016 Nov 17. Erratum in: Cell Stem Cell. 2017 Apr 6;20(4):571

Gene expression profiling at birth characterizing the preterm infant with early onset infection

J Mol Med (Berl) 2017 Feb;95(2):169-180. doi: 10.1007/s00109-016-1466-4

Tamoxifen dosing for Cre-mediated recombination in experimental bronchopulmonary dysplasia

Transgenic Res 2017 Feb;26(1):165-170. doi: 10.1007/s11248-016-9987-8

Principal Investigators

Rory E. Morty

Dr. Rory E. Morty , PhD

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

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


Project group

  • Judith Behnke

    Dr. Judith Behnke

  • Misa Gunjak

    Misa Gunjak

    PhD student

  • Miriam Ruth Heindl

    Miriam Ruth Heindl

    PhD student

  • Thijs A. Lilien

    Thijs A. Lilien

    PhD student

  • Nilifer Cevik

    Nilifer Cevik


  • Aybike Erdogan

    Aybike Erdogan


  • Gabriela Michel

    Gabriela Michel , Technician