Tamdy virus pathogenesis in immunocompetent and immunocompromised mouse models

We have established different mouse infection models to enable investigation of TAMV pathogenesis. Adult BALB/c mice did not exhibit obvious clinical symptoms or signs post-TAMV infection. In contrast, adult type I interferon receptor knock-out (IFNAR-/-) mice - A129 - were found to be susceptible to high-doses of TAMV (104 and 106 TCID50) and all developed severe clinical symptoms and signs, including weight loss, immobility, all of which reached the euthanasia criteria at 4/5 days post-infection (dpi). Viral RNA was detected in peripheral blood and different tissues (heart, liver, spleen, lung, kidney, intestine, and brain) of the infected adult A129 mice, with the highest viral loads in the liver (approximately 108.3 copies/uL). Pathological examination also revealed severe liver damage in the infected A129 mice. In addition, the titers of TAMV-specific IgM and IgG antibodies increased rapidly 4-5 dpi in the infected A129 mice. Analysis of cytokine and chemokine expression changes demonstrated that type I IFN may play an important role in the host defense against viral infection by enhancing IL-10 production. Gene ontology and KEGG analyses showed that liver injury may be associated with virus-induced expression of inflammatory cytokines and chemokines.