Pathology and Transcriptomic Characteristics of Skin Lesions Induced by Mpox Virus in Rabbit

Mpox is a zoonotic disease caused by the mpox virus (MPXV) and characterized by fever, lymphadenopathy, and severe skin lesions. Despite effective containment of the 2022 global mpox pandemic, ongoing severe outbreaks persist in Africa. However, insights into MPXV-induced cutaneous pathogenesis in in vivo models remain scarce. This study investigated the histopathological and molecular signatures of skin lesions induced by MPXV via a rabbit intravenous infection model. Cutaneous lesion development in MPXV-infected rabbits was dose-dependent, with some low-dose-infected animals remaining lesion-free. Viral loads in cutaneous lesions were significantly higher than those in other tissues, and the virus primarily replicated in keratinocytes and fibroblasts but was absent from cutaneous smooth muscle. Pathologically, MPXV-induced skin lesions initially showed epidermal acanthosis with parakeratosis, evolving into pustules with mixed inflammatory cell infiltration. Lesions exhibited typical poxviral hallmarks, including syncytial keratinocytes and guarnieri bodies. MPXV activated genes associated with the cell cycle and drove keratinocytes into S phase. Transcriptomic analysis also revealed that MPXV activated systemic lupus erythematosus pathway in skin. This study advances our understanding of the MPXV-host interactions and provides a reference for subsequent research on MPXV-associated skin lesions.