ICCFGG 2022
#38 Host susceptibility to coronavirus in pet cats: genomic and transcriptomic analysis of Feline Infectious Peritonitis Marsha D Wallace*1,2 , TK Hiron*1,2, S Falcone2, S Binks3,4, J Jiang2, K Hughes5, LJ Kennedy6, A Kipar7, JA Mitchell8, A Psifidi1, R Tarlinton9, CA O’Callaghan2, EN Barker10,11, LJ Davison1,2 * These Authors Contributed equally to this work. mwallace@well.ox.ac.uk 1Clinical Sciences and Services, Royal Veterinary College, Hawkshead Lane, Hatfield, UK, 2Wellcome Centre for Human Genetics, University of Oxford, UK, 3Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, Oxford, UK, 4Department of Neurology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK, 5Queen’s Veterinary School Hospital, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK, 6Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK, 7Institut für Veterinärpathologie, Vetsuisse- Fakultät, Universität Zürich, Switzerland, 8Department of Pathology and Pathogen Biology, The Royal Veterinary College, Hatfield, Hertfordshire, UK, 9Faculty of Medicine and Health Sciences, University of Nottingham, Leicestershire, UK, 10Bristol Veterinary School, University of Bristol, Langford, Bristol, UK, 11The Feline Centre, Langford Vets, Langford, Bristol, UK. Feline coronavirus (FCoV) is a contagious virus ubiquitous in most cat populations. In a small percentage of infected cats, an aberrant immune response to FCoV and change in tropism of the virus, allowing it to infect and replicate in macrophages, results in Feline Infectious Peritonitis (FIP), which is fatal without anti-viral therapy (e.g. remdesivir). FIP pathogenesis is complex, and it is unclear why some cats develop FIP, while others do not. Some breeds more commonly develop FIP, suggesting a genetic component to host susceptibility. The parallels between FIP and COVID-19 (fatal coronavirus infections with shared treatments) make FIP an important disease to study coro- navirus host susceptibility. The MASCOT (Mapping Animal Susceptibility to Coronaviruses: Outcomes and Transcriptomics) consortium has undertaken genomic and transcriptomic studies of UK cats with and without FIP. RNA-Seq analysis comparing cats with naturally occurring FIP to controls showed differentially expressed genes in lung, liver, and mesenteric lymph nodes associated with anti-virus and inter- feron responses. Whole genome sequencing of cats (12 FIP, 12 controls) and targeted follow-up genotyping (66 FIP, 39 controls) identified candidate variants associated with FIP, several of which reside in immune response genes, including interferon-stimulated genes (ISGs), and impact COVID-19 severity in humans. Validation in an additional cohort of cats is underway. Together, these results suggest a critical role for the host immune response and type 1 interferons in FIP pathogenesis. Understanding the importance of specific genes and mechanisms in FIP provides opportunities for new strategies for treatment and prevention of coronavirus-related diseases.
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