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A Cell Culture Model for Producing High Titer Hepatitis E Virus Stocks
Published on: June 26, 2020
Virulent strain of hepatitis E virus genotype 3, Japan
Kazuaki Takahashi1, Hiroaki Okamoto, Natsumi Abe
1Toshiba General Hospital, Tokyo, Japan. kazuaki6.takahashi@po.toshiba.co.jp
Abstract:
Hepatitis E virus (HEV) genotype 3, which usually causes asymptomatic infection in Japan, induced severe hepatitis in 8 patients. To better understand genetic features of HEV associated with increased virulence, we determined the complete or near-complete nucleotide sequences of HEV from these 8 patients and from 5 swine infected with genotype 3 strain swJ19. Phylogenetic analysis showed that the isolates from the 8 patients and the 5 swine grouped separately from the other genotype 3 isolates to create a unique cluster, designated JIO. The human JIO-related viruses encoded 18 amino acids different from those of the other HEV genotype 3 strains. One substitution common to almost all human HEV strains in the JIO cluster was located in the helicase domain (V239A) and may be associated with increased virulence. A zoonotic origin of JIO-related viruses is suspected because the isolates from the 5 swine also possessed the signature V239A substitution in helicase.
Insights
Hepatitis E virus (HEV) genotype 3 caused severe hepatitis in Japan. A unique HEV cluster (JIO) found in patients and swine, featuring a V239A substitution, may explain this increased virulence.
Area of Science:
- Virology
- Infectious Diseases
- Genetics
Background:
- Hepatitis E virus (HEV) genotype 3 typically causes asymptomatic infections in Japan.
- Recent cases indicate HEV genotype 3 can induce severe hepatitis, prompting investigation into virulence factors.
Purpose of the Study:
- To determine the genetic features of HEV associated with increased virulence in severe hepatitis cases.
- To investigate the phylogenetic relationship and potential zoonotic origin of virulent HEV genotype 3 strains.
Main Methods:
- Sequencing of complete or near-complete nucleotide genomes of HEV from 8 patients and 5 infected swine.
- Phylogenetic analysis to identify unique viral clusters and genetic variations.
- Comparative analysis of amino acid sequences between virulent and non-virulent HEV strains.
Main Results:
- HEV isolates from patients and swine formed a distinct phylogenetic cluster, designated JIO, separate from other genotype 3 strains.
- JIO cluster viruses exhibited 18 unique amino acid substitutions compared to other genotype 3 HEV strains.
- A common V239A substitution in the helicase domain was identified in JIO cluster viruses, potentially linked to increased virulence.
Conclusions:
- A unique HEV genotype 3 cluster (JIO) associated with severe hepatitis has been identified.
- The V239A substitution in the helicase domain is a potential marker for increased HEV virulence.
- The presence of the V239A substitution in both human and swine isolates suggests a zoonotic origin for JIO-related viruses.
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