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March 21, 2026PLoS Pathogens0 citationsOpen Access

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

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HZHe ZhangYWYang WuHWH. X. Wang

Key Result

Three wild rodent species, particularly Apodemus peninsulae, are susceptible to Hepatitis E virus genotype 1 infection, exhibiting systemic viral replication and mild liver pathology.

Key Points

  • To investigate whether wild rodents can be natural hosts for hepatitis E virus genotype 1 (HEV-1).
  • Infected three rodent species with HEV-1 through oral gavage inoculation.
  • Monitored fecal viral shedding and systemic replication.
  • Conducted transcriptomic analysis of liver tissue to assess inflammatory response.
  • Applied ribavirin treatment to evaluate its effect on viral replication.
  • Rodent species A. peninsulae showed the highest susceptibility to HEV-1 infection.
  • Infected rodents exhibited viral shedding, seroconversion, and mild liver pathology.
  • Intrahepatic analysis revealed upregulation of inflammatory markers IL-1β and IL-18.
  • Ribavirin was effective in suppressing viral replication.

Structured PICO

Can wild rodents serve as potential hosts for Hepatitis E virus genotype 1?

P
Population
Three wild rodent species (Apodemus peninsulae, Clethrionomys rufocanus, and Lasiopodomys brandtii)
I
Intervention
Hepatitis E virus genotype 1 (HEV-1) infection
O
Outcome
Susceptibility to HEV-1 infection (viral shedding, replication, seroconversion, liver pathology)surrogate

Wild rodents, particularly A. peninsulae, are susceptible to HEV-1 infection, suggesting they could serve as potential hosts and play a role in its ecology and cross-species transmission.

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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Cite This Study

Zhang et al. (2026) studied this question. Three wild rodent species, particularly Apodemus peninsulae, are susceptible to Hepatitis E virus genotype 1 infection, exhibiting systemic viral replication and mild liver pathology.

synapsesocial.com/papers/69be35606e48c4981c6739cdhttps://doi.org/10.1371/journal.ppat.1014050
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