Tamdy virus pathogenesis in immunocompetent and immunocompromised mouse models.

Tamdy virus (TAMV) is one of the 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 knockout (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 and immobility, and reached the euthanasia criteria at 4/5-day post-infection (dpi). Viral RNA was detected in peripheral blood and different tissues (heart, liver, spleen, lung, kidney, intestine, and brain) of the high-dose 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 high-dose infected A129 mice. In addition, the titres 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 defence 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. Together, we have investigated TAMV pathogenesis using immunocompetent and immunocompromised mouse models, which will facilitate the development of TAMV-specific antivirals and vaccines.