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Viruses with RNA Genomes01:29

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RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
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Persistent infection with a rabbit hepatitis E virus created by a reverse genetics system.

Wenjing Zhang1, Yasushi Ami2, Yuriko Suzaki2

  • 1Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.

Transboundary and Emerging Diseases
|July 11, 2020
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Researchers developed a reverse genetics system for rabbit hepatitis E virus (HEV), creating infectious HEV in cell culture. This breakthrough enables further study of HEV replication and pathogenesis.

Keywords:
persistent infectionrabbit HEVrabbit hepatitis E virusreverse genetics systemzoonotic infection

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Area of Science:

  • Virology
  • Infectious Diseases
  • Molecular Biology

Background:

  • Rabbit hepatitis E virus (HEV) is a novel zoonotic pathogen.
  • Existing cell culture systems allow HEV propagation but lack a reverse genetics system for generating infectious virus.

Purpose of the Study:

  • To establish a reverse genetics system for rabbit HEV.
  • To generate infectious rabbit HEV in cell culture.
  • To evaluate the potential of ribavirin as a therapeutic agent and the rabbit as an animal model for HEV infection.

Main Methods:

  • In vitro transcription of capped genomic rabbit HEV RNAs.
  • Transfection of RNAs into PLC/PRF/5 cells and subsequent virus recovery and passaging.
  • Infection of rabbits via intravenous and oral inoculation with cell culture-derived HEV.
  • Genome-wide sequence analysis of recovered viruses.
  • In vitro and in vivo evaluation of ribavirin efficacy.
  • Assessment of persistent infection and disease development in rabbits.

Main Results:

  • A functional reverse genetics system for rabbit HEV was successfully established.
  • Infectious rabbit HEV was generated in cell culture and confirmed to be pathogenic in rabbits.
  • No nucleotide sequence changes were observed in recovered viral genomes.
  • Ribavirin demonstrated efficient ex vivo inhibition and transient in vivo suppression of HEV replication.
  • Rabbit HEV infection led to persistent infection in rabbits, establishing a potential animal model.

Conclusions:

  • The developed reverse genetics system is crucial for studying rabbit HEV replication mechanisms and viral hepatitis pathogenesis.
  • Infectious rabbit HEV generated in vitro can cause disease in vivo, validating its utility.
  • Ribavirin shows promise as a potential therapeutic candidate for HEV infections.
  • The infected rabbit serves as a valuable animal model for HEV-induced hepatitis research.