CAST/EiJ and NOG mice as lethal animal models for a 2022 human isolate of monkeypox virus Clade IIb

The monkeypox virus (MPXV) outbreak has caused more than 150,000 infections worldwide since May 2022. The strain MPXV-ROK-P1-2022, isolated from the first patient in South Korea, belongs to the B.1.1 lineage of Clade IIb. To assess whether CAST/EiJ and NOG mice are suitable models for MPXV Clade IIb infection, we experimentally infected these mice with MPXV-ROK-P1-2022 and monitored clinical symptoms and body weight. For polymerase chain reaction, plaque assay, and histopathology, blood, lung, liver, spleen, testis, and brain tissues were collected. The results showed dose dependent lethality, and the virus established a systemic infection, replicating in multiple organs. Viral replication and DNA levels were exceptionally high in the testes. CAST/EiJ mice exhibited enlarged spleens with lymphoid depletion and scattered cellular necrosis. In summary, intraperitoneal challenge with the MPXV-ROK-P1-2022 Clade IIb strain causes a lethal, systemic infection in CAST/EiJ and NOG mice. The pronounced viral tropism for the testes highlights their potential as a model for studying MPXV pathogenesis and organ tropism and evaluating vaccine efficacy.