Essential Role of Interferon Response in Containing Human Pathogenic Bourbon Virus

Bourbon virus (BRBV) is a recently discovered tick-transmitted viral pathogen that is prevalent in the Midwest and southern United States. Since 2014, zoonotic BRBV infections have been verified in several human cases of severe febrile illness, occasionally with fatal outcomes, indicating a possible public health threat. We analyzed the pathology of BRBV infection in mice and found a high sensitivity of the virus to the host interferon system. Infected standard laboratory mice did not show clinical signs or virus replication. However, in mice carrying defects in the type I and type II interferon system, the virus grew to high titers and caused severe pathology. In cell culture, BRBV was blocked by antiviral agents like ribavirin and favipiravir (T705). Our data suggest that persons having severe BRBV infection might have a deficiency in their innate immunity and could benefit from an already approved antiviral treatment.