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

doi:10.3390/v15040993

A Multimodal Imaging-Supported Down Syndrome Mouse Model of RSV Infection

Viruses. 2023 Apr 18;15(4):993. doi: 10.3390/v15040993.

Affiliations

¹ Biomedical MRI Unit/Mosaic, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium.
² Laboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium.
³ Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium.
⁴ Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven, 3000 Leuven, Belgium.
⁵ Radiomics (Oncoradiomics SA), 4000 Liege, Belgium.
⁶ Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, 3000 Leuven, Belgium.

Abstract

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.

Keywords: DS immunity; Down syndrome; RSV development; Ts65Dn mouse model; non-invasive imaging; respiratory infections.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Disease Models, Animal
Down Syndrome* / pathology
Humans
Lung / pathology
Mice
Multimodal Imaging
Respiratory Syncytial Virus Infections*
Respiratory Syncytial Virus, Human*

Grants and funding

This research work received financial support from the Jerome Lejeune Foundation (“Cardiopulmonary-vascular disorders in Down syndrome research: a long-overlooked issue”). B.T. received a postdoctoral fellowship from the Sisley-d’Ornano Foundation and the Jerome Lejeune Foundation. L.S. (1186121N) is supported by a FWO-SB fellowship and E.P. is a recipient of the L’Oréal-Unesco Women for Sciences PhD fellowship.