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Updated: Dec 15, 2025
A Cell Culture Model for Producing High Titer Hepatitis E Virus Stocks
Published on: June 26, 2020
Characterization of a Novel Rat Hepatitis E Virus Isolated from an Asian Musk Shrew (Suncus murinus)
Huimin Bai1, Wei Li2, Dawei Guan2
1Department of Basic Medicine and Forensic Medicine, Baotou Medical College, Jianshe Road 31, Baotou 014060, China.
Abstract:
The Asian musk shrew (shrew) is a new reservoir of a rat hepatitis E virus (HEV) that has been classified into genotype HEV-C1 in the species Orthohepevirus C. However, there is no information regarding classification of the new rat HEV based on the entire genome sequences, and it remains unclear whether rat HEV transmits from shrews to humans. We herein inoculated nude rats (Long-Evans rnu/rnu) with a serum sample from a shrew trapped in China, which was positive for rat HEV RNA, to isolate and characterize the rat HEV distributed in shrews. A rat HEV strain, S1129, was recovered from feces of the infected nude rat, indicating that rat HEV was capable of replicating in rats. S1129 adapted and grew well in PLC/PRF/5 cells, and the recovered virus (S1129c1) infected Wistar rats. The entire genomes of S1129 and S1129c1 contain four open reading frames and share 78.3-81.8% of the nucleotide sequence identities with known rat HEV isolates, demonstrating that rat HEVs are genetically diverse. We proposed that genotype HEV-C1 be further classified into subtypes HEV-C1a to HEV-C1d and that the S1129 strain circulating in the shrew belonged to the new subtype HEV-C1d. Further studies should focus on whether the S1129 strain infects humans.
Insights
Asian musk shrews harbor a novel rat hepatitis E virus (HEV) strain, HEV-C1d. This study confirms rat HEV replication in rats and proposes new HEV-C1 subtypes, highlighting potential zoonotic transmission risks.
Area of Science:
- Virology
- Zoonotic Diseases
- Genomics
Background:
- The Asian musk shrew is identified as a new reservoir for rat hepatitis E virus (HEV), classified under genotype HEV-C1 within Orthohepevirus C.
- Existing classification of rat HEV lacks comprehensive genomic data, and its transmission potential to humans remains uninvestigated.
Purpose of the Study:
- To isolate and characterize rat HEV strains found in shrews.
- To determine if rat HEV can replicate in rats and to analyze the genetic diversity of these viruses.
- To propose a refined classification for HEV-C1 based on genomic sequences.
Main Methods:
- Inoculation of nude rats with shrew-derived rat HEV RNA.
- Isolation and adaptation of the virus in cell cultures (PLC/PRF/5).
- Infection of Wistar rats with the adapted virus.
- Whole-genome sequencing and phylogenetic analysis of recovered rat HEV strains.
Main Results:
- A novel rat HEV strain, S1129, was successfully isolated from feces of infected nude rats, confirming replication in rats.
- The S1129 strain adapted and replicated in cell culture (S1129c1) and subsequently infected Wistar rats.
- Genomic analysis revealed significant genetic diversity among rat HEVs, with S1129 belonging to a proposed new subtype, HEV-C1d.
Conclusions:
- Rat HEV demonstrates genetic diversity and can replicate within rodent hosts.
- The study proposes a further classification of genotype HEV-C1 into subtypes HEV-C1a to HEV-C1d.
- Further research is warranted to assess the zoonotic potential of the S1129 strain and its implications for human health.
