Mucosal Sudan virus infection results in a lethal disease in ferrets with previous Lloviu virus infection not providing cross-protection.

Sudan virus (SUDV) causes highly lethal outbreaks of hemorrhagic disease throughout Africa, but there has yet to be an approved vaccine or therapeutic to combat this public health threat. The most common route of natural exposure to filoviruses is through mucosal contact which greatly impacts initial viral replication. Historically, SUDV animal models used an intramuscular infection route. Here, we sought to further characterize an animal model using mucosal challenge routes and compared the impact that intramuscular, intranasal, or aerosol exposure had on SUDV pathogenicity in a ferret model. We determined that the route of infection did not significantly impact overall SUDV pathogenicity; only subtle changes were detected in magnitude of viremia and oral viral shedding. Additionally, we sought to determine if preexisting Lloviu virus (LLOV) immunity could protect ferrets from lethal SUDV infection. We found that the previous immunity elicited by LLOV infection was not sufficient to protect ferrets from lethal SUDV disease. In conclusion, our results indicate that the infection route has minimal effect on overall pathogenicity of SUDV in ferrets and that prior LLOV infection does not elicit a cross-protective immune response to SUDV.