KFO309 - The clinical research unit Virus Induced Lung injury

Principal Investigators

Susanne Herold

Prof. Dr. med. Susanne Herold , PhD

Coordinator

Justus Liebig University
Department of Internal Medicine II
Klinikstr. 33; 35392 Giessen

+49-641-985-42552
Stephan Becker

Prof. Dr. rer. nat. Stephan Becker

Philipps-University-Marburg
Institute of Virology
Hans-Meerwein-Str. 2; 35043 Marburg

+49-6421-28-66253
Christin Peteranderl

Christin Peteranderl , geb. Becker, PhD

Justus Liebig University Giessen
Department of Medicine II,
Klinikstr. 33; 35392 Giessen

Targeting immunophilin- and MAPK-associated pathways to inhibit MERS-CoV replication and prevent inflammatory lung injury

Summary

Coronaviruses (CoV) are causative agents of acute lung injury, and it is expected that novel highly pathogenic CoV will infect humans in future. However, drugs providing protection against emerging human CoV (such as MERS-CoV), are lacking. By use of a novel MERS-CoV mouse infection model and primary human lung cells, we aim to define the antiviral and lung injury-attenuating properties of compounds known to block CoV-host interactions by targeting immunophilin and downstream MAPK pathways in vitro and in vivo to establish readily-available treatment strategies for ongoing and future emerging severe human CoV infections.

Combining knowledge in the fields of molecular pathogenesis of acute lung injury gained in animal models and in patients suffering from severe respiratory virus infections, and virology expertise in research of highly pathogenic viruses under BSL4 conditions, the project aims at i) defining in detail the molecular host-virus interactions related to immunophilin-mediated blockade of MERS-CoV replication, ii) characterizing how MERS-CoV viral replication results in loss of barrier integrity and lung injury, and how these processes can be targeted to attenuate the disease progression in vivo, and iii) evaluating the role of transcriptional programs downstream of immunophilins (e.g. NFAT- and AP-1-dependent programs), in MERS-CoV-induced immunopathology, and their exploitation as therapeutic targets to decrease damaging hyperinflammation. To achieve this, we will use complementary murine and human in vitro, ex vivo and in vivo MERS-CoV infection models, using both inhibitory compounds affecting immunophilin-dependent signaling, and transgenic mice lacking crucial signaling components of these pathways. These studies will be complemented by NGS analyses of FACS-separated and infected lung cell subsets, for novel target identification.

The obtained data are expected to ultimately pave the way for development of novel antiviral and lung injury-attenuating compounds for treatment of MERS-CoV and, putatively, a broad range of human-pathogenic CoV.

Publications





Digital Image Analyses on Whole-Lung Slides in Mouse Models of Acute Pneumonia

AJRCMB 2018 58(4):440-448 doi: 10.1165/rcmb.2017-0337MA10.1165/rcmb.2017-0337MA




Principal Investigators

Susanne Herold

Prof. Dr. med. Susanne Herold , PhD

Coordinator

Justus Liebig University
Department of Internal Medicine II
Klinikstr. 33; 35392 Giessen

+49-641-985-42552
Stephan Becker

Prof. Dr. rer. nat. Stephan Becker

Philipps-University-Marburg
Institute of Virology
Hans-Meerwein-Str. 2; 35043 Marburg

+49-6421-28-66253
Christin Peteranderl

Christin Peteranderl , geb. Becker, PhD

Justus Liebig University Giessen
Department of Medicine II,
Klinikstr. 33; 35392 Giessen

Project group

  • Lucie Sauerhering

    Dr. Lucie Sauerhering

    Postdoc

    +49-6421-28-65159
  • Hosam Shams-Eldin

    Dr. Hosam Shams-Eldin

    Veterinarian

  • Alexandra Kupke

    Dr. Alexandra Kupke

    Veterinarian

  • Blanche Nganko

    Blanche Nganko

    MD student

    +49-641-985-42712
  • Stefanie Jarmer

    Stefanie Jarmer

    Technician

    +49-641-985-42712
  • Katharina Kowalski

    Katharina Kowalski

    Technician