Mathematical models of Usutu virus infection

Usutu virus is a mosquito-borne virus maintained in wild bird populations, which leads to mosquito infections, and occasional spillover in humans. It has been hypothesized that increased Usutu virus replication in birds and/or decreased bird immune competence leads to increased mosquitoes infection and increased transmission to humans. To provide insight into the intrinsic complexity of host-virus processes in birds, we developed mathematical models of Usutu virus infection and fitted them against four Usutu virus strains data from chicken infections. We have also investigated the effect of antibody on virus dynamics by fitting the models to chickens that were genetically engineered to have low and high antibody count. Parameter distributions for virus production, virus replication, host responses, and basic reproduction number were generated using non-linear mixed-effects models. We observed differences in virulence amongst the four virus strains, and found that birds with high antibody count have higher infected cell killing and higher virus clearance rates, indicative of non-neutralizing antibody function. These results can be used to better determine which virus strain is the most likely to spillover in the human population.