Marin Habbick, VIDO, University of Saskatchewan

Marin Habbick1,2, Reema Singh2, Stephanie L. Saundh2, Angela L. Rasmussen1,2 1 Vaccine and Infectious Disease Organization, University of Saskatchewan 2 Department of Biochemistry, Immunology and Microbiology, University of Saskatchewan

Fighting & Responding

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic coronavirus capable of causing lethal illness in humans; however, some individuals exhibit tolerance to infection, displaying mild or asymptomatic disease. Although sex-specific MERS-CoV disease outcomes have been observed, sex is a poorly understood determinant of pathogenicity. Sex bias during infection can result from distinct responses to infection by sex-linked gene expression, sex hormones, or anatomical and physiological variations; however, the specific mechanisms underlying sex biases in infection and pathogenesis are unknown. This project will investigate the mechanistic basis of two primary sex hormones, 17β-estradiol (E2) and dihydrotestosterone, in determining tolerance to highly pathogenic human coronavirus infection. We have analyzed transcriptomic data collected from mice infected with a tolerant low-dose or lethal high-dose of MERS-CoV and found that sex bias impacts the kinetics and magnitude of the host response as well as the outcome to infection. To further investigate the impact of sex hormones in vitro, we have treated hormone-responsive HEK293T cells with E2 then infected with MERS-CoV to observe the effects on viral replication and host antiviral signalling. This study provides the first insights into sex bias in MERS-CoV infection both in vivo and in vitro. By examining the role of sex in determining viral fitness and disease severity, this study will advance our understanding of sex hormones as a biological variable in coronavirus pathogenesis research.