A Multimodal Imaging-Supported Down Syndrome Mouse Model of RSV Infection
Birger Tielemans,
Lander De Herdt,
Emilie Pollenus,
Emiel Vanhulle,
Laura Seldeslachts,
Fopke Marain,
Flore Belmans,
Kaveh Ahookhosh,
Jeroen Vanoirbeek,
Kurt Vermeire,
Philippe E. Van den Steen,
Greetje Vande Velde
Affiliations
Birger Tielemans
Biomedical MRI Unit/Mosaic, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium
Lander De Herdt
Biomedical MRI Unit/Mosaic, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium
Emilie Pollenus
Laboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium
Emiel Vanhulle
Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium
Laura Seldeslachts
Biomedical MRI Unit/Mosaic, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium
Fopke Marain
Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven, 3000 Leuven, Belgium
Flore Belmans
Biomedical MRI Unit/Mosaic, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium
Kaveh Ahookhosh
Biomedical MRI Unit/Mosaic, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium
Jeroen Vanoirbeek
Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, 3000 Leuven, Belgium
Kurt Vermeire
Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium
Philippe E. Van den Steen
Laboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium
Greetje Vande Velde
Biomedical MRI Unit/Mosaic, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium
Individuals with Down syndrome (DS) are more prone to develop severe respiratory tract infections. Although a RSV infection has a high clinical impact and severe outcome in individuals with DS, no vaccine nor effective therapeutics are available. Any research into infection pathophysiology or prophylactic and therapeutic antiviral strategies in the specific context of DS would greatly benefit this patient population, but currently such relevant animal models are lacking. This study aimed to develop and characterize the first mouse model of RSV infection in a DS-specific context. Ts65Dn mice and wild type littermates were inoculated with a bioluminescence imaging-enabled recombinant human RSV to longitudinally track viral replication in host cells throughout infection progression. This resulted in an active infection in the upper airways and lungs with similar viral load in Ts65Dn mice and euploid mice. Flow cytometric analysis of leukocytes in lungs and spleen demonstrated immune alterations with lower CD8+ T cells and B-cells in Ts65Dn mice. Overall, our study presents a novel DS-specific mouse model of hRSV infection and shows that potential in using the Ts65Dn preclinical model to study immune-specific responses of RSV in the context of DS and supports the need for models representing the pathological development.
