Development of a Deer Tick Virus Infection Model in C3H/HeJ Mice to Mimic Human Clinical Outcomes

Deer tick virus (DTV) is a Tick-Borne Orthoflavivirus endemic to the United States, transmitted to humans through bites from the deer tick, Ixodes scapularis, which is also the primary vector of Borrelia burgdorferi s.l., the causative agent of Lyme disease. Human infection with DTV can result in acute febrile illness followed by central nervous system complications, such as encephalitis and meningoencephalitis. Currently, there are mouse models established for investigating the pathogenesis and clinical outcomes of DTV that mimic human infections, but the strains of mice utilized are refractory to infection with B. burgdorferi s.l. Here, we describe the pathogenesis and clinical outcomes of DTV infection in C3H/HeJ mice. Neurological clinical signs, mortality, and weight loss were observed in all DTV-infected mice during the investigation. Infected animals demonstrated consistent viral infection in their organs. Additionally, neuropathology of brain sections indicated the presence of meningoencephalitis throughout the brain. This data, along with the clinical outcomes for the mice, indicates successful infection and showcases the neuroinvasive nature of the virus. This is the first study to identify C3H/HeJ mice as an appropriate model for DTV infection. As C3H/HeJ mice are already an established model for B. burgdorferi s.l. infection, this model could serve as an ideal system for investigating disease progression and pathogenesis of co-infections.