Modelling the effect of genotype (PRNP) linked to susceptibility, infection duration and prion shedding on chronic wasting disease dynamics of cervids

Host genetics affect their susceptibility to pathogens and their ability to transmit infections (contagiousness). Chronic wasting disease (CWD) is a lethal prion disease of cervids with a wide distribution in North America, and with the first detection in Europe among reindeer in Norway in 2016. The PRNP gene, encoding the prion protein, has a strong impact on host susceptibility, and the duration and level of prion shedding. We developed a Susceptible-Exposed-Infectious-Dead (SEID) model to enhance our understanding of how PRNP genotype variation influences CWD dynamics. In a baseline model with only highly susceptible PRNP alleles, CWD prevalence reached a high level before the population collapsed. We sequentially introduced PRNP heterogeneity in susceptibility (Scenario 1), the duration of prion shedding (Scenario 2), and amount of prion shedding (Scenario 3). Heterogeneity in susceptibility alone (Scenario 1) led to a slow increase in CWD prevalence towards its peak, followed by a gradual decline and eventual epidemic die-out. Increasing the infection duration with constant shedding for the less susceptible PRNP genotypes (Scenario 2) led to a high and persistent CWD-prevalence level. When combining low-susceptibility PRNP alleles and increased duration of shedding but at lower levels (Scenario 3), the prevalence of CWD peaked slowly compared to the other scenarios. Hence, variation in PRNP allele composition can yield qualitatively different CWD epidemics among populations. Our ability to predict the long-term effects of CWD remains limited, primarily due to uncertainty about shedding patterns, environmental contamination, and other factors associated with PRNP-alleles that may limit selection.