In a panel of inbred strains of mice, RSV disease phenotypes were characterized that resemble those in human disease.
We identified Marco as a susceptibility gene, and a human MARCO mutation increased risk of disease severity in children.
These studies have implications for diagnosing individuals who are at risk for severe RSV disease and prevent disease.
RSV disease is the primary global cause for hospitalization one year after birth but the causes of differential RSV disease severity are not understood. We show that RSV disease phenotypes vary significantly between inbred strains of mice, and resemble those in human disease. We used genetic approaches to identify and validate the innate immunity gene Marco as a host susceptibility determinant for murine RSV disease. We then characterized a loss of function polymorphism in human MARCO that increases risk of severe RSV disease risk in infants. Results have important implications for identifying genetic risk factors for severe RSV disease.