The Full-Genome Analysis and Generation of an Infectious cDNA Clone of a Genotype 6 Hepatitis E Virus Variant Obtained from a Japanese Wild Boar: In Vitro Cultivation in Human Cell Lines.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI
    • Subject Terms:
      Genome, Viral* ; Hepatitis E*/virology ; Hepatitis E*/veterinary ; Hepatitis E*/transmission ; Hepatitis E virus*/genetics ; Hepatitis E virus*/classification ; Hepatitis E virus*/isolation & purification ; Phylogeny* ; Sus scrofa*/virology; Animals ; Cell Line ; DNA, Complementary/genetics ; Genotype ; Japan ; RNA, Viral/genetics ; Swine ; Swine Diseases/virology ; Swine Diseases/transmission
    • Abstract:
      Hepatitis E virus (HEV) can cause self-limiting acute and chronic hepatitis infections, particularly in immunocompromised individuals. In developing countries, HEV is mainly transmitted via drinking contaminated water, whereas zoonotic transmission dominates the route of infection in developed countries, including Japan. Pigs are an important reservoir for HEV infection. Wild boars, which share the same genus and species as domestic pigs, are also an HEV reservoir. During our nationwide study of HEV infection in wild boar populations in Japan, a genotype 6 (HEV-6) strain, wbJHG_23, was isolated in Hyogo Prefecture in 2023. The genomic length was 7244 nucleotides, excluding the poly(A) tract. The wbJHG_23 strain exhibited the highest nucleotide identity throughout its genome with two previously reported HEV-6 strains (80.3-80.9%). Conversely, it displayed lower similarity (73.3-78.1%) with the HEV-1-5, HEV-7, and HEV-8 strains, indicating that, although closely related, the wbJHG_23 strain differs significantly from the reported HEV-6 strains and might represent a novel subtype. The wbJHG_23 strain successfully infected the human-derived cancer cell lines, PLC/PRF/5 and A549 1-1H8 cells, suggesting that HEV-6 has the potential for zoonotic infection. An infectious cDNA clone was constructed using a reverse genetics system, and a cell culture system supporting the efficient propagation of the HEV-6 strain was established, providing important tools for further studies on this genotype. Using this cell culture system, we evaluated the sensitivity of the wbJHG_23 strain to ribavirin treatment. Its good response to this treatment suggested that it could be used to treat human infections caused by HEV-6.
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    • Grant Information:
      JP23fk0210132 Japan Agency for Medical Research and Development; JP24fk0210132 Japan Agency for Medical Research and Development; 22K15478 Japan Society for the Promotion of Science
    • Contributed Indexing:
      Keywords: HEV-6 variant; cell culture; hepatitis E virus; infectious cDNA clone; reverse genetics; wild boar
    • Accession Number:
      0 (DNA, Complementary)
      0 (RNA, Viral)
    • Publication Date:
      Date Created: 20240627 Date Completed: 20240627 Latest Revision: 20240629
    • Publication Date:
      20240629
    • Accession Number:
      PMC11209168
    • Accession Number:
      10.3390/v16060842
    • Accession Number:
      38932135