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

TL;DR

Researchers found that three wild rodent species can be infected with a human-specific hepatitis E virus, suggesting these animals might play a role in virus spread.

Contribution

The study identifies wild rodents as potential natural hosts for HEV-1, challenging the belief that the virus is strictly human-specific.

Findings

Apodemus peninsulae showed high susceptibility to HEV-1 with symptoms similar to human infections.

Infected rodents exhibited systemic viral replication and activated inflammatory pathways like IL-1β and IL-18.

HEV-1 can be transmitted through oral, contact, and vertical routes in these rodents, with ribavirin effective in suppressing replication.

Abstract

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.

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