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Canine distemper virus (CDV) infects a broad range of carnivores and causes a highly contagious disease with severe immunosuppression.The disease severity markedly varies in different species.To investigate the pathogenesis of CDV in raccoon dog (Nyctereutes procyonoides), fox (Vulpes vulpes) and mink (Neovison vison) species, three groups of CDV sero-negative animals were infected with CDV strain LN(10)1.This CDV strain belongs to the Asia-1 genotype, which is epidemiologically predominant in carnivores in China.CDV infection provoked marked differences in virulence in the three species that were studied.Raccoon dogs developed fever, severe conjunctivitis, and pathological lesions, with 100% (5/5)mortality and with high viral RNA loads in organs within 15 days post infection (dpi).In infected foxes, the onset of the disease was delayed, with 40% (2/5) mortality by 21dpi.Infected minks developed only mild clinical signs and pathological lesions, and mortality was not observed.Raccoon dogs and foxes showed more severe immune suppression (lymphopenia,decreased lymphocyte proliferation, viremia and low-level virus neutralizing antibodies) than minks.We also observed a distinct pattern of cytokine mRNA transcripts at different times after infection.Decreased IFN-γand IL-4 mRNA responses were evident in the animals with fatal disease, while up-regulation of these cytokines was observed in the animals surviving the infection.Increased TNF-α response was detected in animals with mild or severe clinical signs.Based on the results, we could distinguish three different patterns of disease after experimental CDV infection, e.g.a mild form in minks, a moderate form in foxes and a severe disease in raccoon dogs.The observed differences in susceptibility to CDV could be related todistinct host cytokine profiles.Comparative evaluation of CDV pathogenesis in various animal species is pivotal to generate models suitable for the evaluation of CDV-host interactions and of vaccine response.