Supplemental information 2.xlsx

Tamdy virus (TAMV) is one of a number of zoonotic tick-borne bunyaviruses that have emerged as global public health threats in recent decades. To date, however, TAMV pathogenesis remains poorly understood. In the present study, 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^-/-) A129 mice were found to be susceptible to high-doses of TAMV (6×10² and 6×10⁴ FFU) and all developed severe clinical symptoms and signs, including weight loss, immobility, and 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 10^8.3 copies/μL). 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. 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 cytokinesand chemokines.Together, we have investigated TAMV pathogenesis using immunocompetent and immunocompromised mouse models, which should help facilitate the development of TAMV-specific antivirals and vaccines.