A pan-orthohantavirus human lung xenograft mouse model and its utility for preclinical studies
Author summary Orthohantaviruses are rodent-borne pathogens that can be transmitted from rodents to humans by inhalation of aerosolized virus-contaminated rodent excreta. While orthohantaviruses generally do not cause overt clinical signs in rodents, orthohantavirus infection can lead to severe disease with case fatality rates up to 40%. The pathogenesis of associated hemorrhagic fever with renal syndrome (HFRS) mainly in Europe and Asia and hantavirus cardiopulmonary syndrome (HCPS) in the Americas remains poorly understood. Particularly the understanding of the early steps of pathogenesis occurring in the human lungs is limited. In addition, assessment of the efficacy of cross-reactive anti-orthohantavirus antibodies is severely hampered by the limited availability of in vivo models that allow for replication of both HFRS- and HCPS-associated orthohantaviruses within the same animal model. Therefore, we present a human lung xenograft mouse model to study early events of orthohantavir
