Experimental hepatitis E virus genotype 1 infection in three types of wild rodents

Hepatitis E virus genotype 1 (HEV-1) has long been considered human-specific, with no known natural animal hosts. Here, we demonstrate that three wild rodent species-Apodemus peninsulae, Clethrionomys rufocanus, and Lasiopodomys brandtii-are susceptible to HEV-1 infection. Among them, A. peninsulae infected with HEV-1 exhibited the highest susceptibility, characterized by robust fecal viral shedding, systemic viral replication, seroconversion, and mild liver pathology mimicking human acute HEV-1 infection. Intrahepatic transcriptomic analysis of infected animals revealed activation of inflammatory pathways, including upregulation of IL-1β and IL-18. Re-inoculation experiments confirmed infection-induced protective immunity, and ribavirin treatment effectively suppressed viral replication. HEV-1 infection can be established by oral gavage inoculation, close contact and vertical transmission. These results provide solid evidence that wild rodents can serve as potential hosts for HEV-1, highlighting the potential role of wild rodents in HEV-1 ecology and cross-species transmission.