Human febrile illness associated with Yanggou tick virus: Clinical characteristics and epidemiological links to rodents

Objectives We identified Yanggou tick virus (YGTV), a segmented flavivirus previously unrecognized as a human pathogen, in a patient presenting with fever and headache. This study aims to characterize the epidemiology and clinical manifestations of YGTV infection in patients with fever of unknown origin (FUO). Methods We conducted a surveillance study at the First Hospital of Jilin University (2020–2025) involving 1,011 patients with FUO. Concurrently, ticks and rodents in the vicinity of the patients' residences and workplaces were collected for viral detection. YGTV infection was confirmed via PCR assays. Positive samples were used for viral isolation, genome amplification, and phylogenetic characterization. An Apodemus agrarius challenge model was established to evaluate viral persistence and shedding. Results Of the 30 confirmed cases of YGTV infection, 10 were co-diagnosed with hemorrhagic fever with renal syndrome (HFRS). The patients showed no clear seasonality or geographic bias. Notably, rodent contact (43.3%) was a more frequent risk factor than tick bites (6.7%). While clinical presentations were non-specific, nearly 50% of the patients presented with gastrointestinal and neurological symptoms. YGTV was isolated from patients, ticks, and A. agrarius (the latter often co-infected with Hantaan virus). Animal models confirmed persistent splenic infection and viral shedding via oral and fecal routes. Conclusion Our findings establish YGTV as an underdiagnosed cause of human febrile illness, underscoring the transmission risks posed by tick vectors and rodent reservoirs. These results highlight the urgent need for enhanced clinical surveillance and diagnostic screening among patients presenting with FUO, particularly in regions where the virus is endemic.