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Journal of virology2014; 88(22); 13352-13366; doi: 10.1128/JVI.02280-14

Hallmarks of hepatitis C virus in equine hepacivirus.

Abstract: Equine hepacivirus (EHcV) has been identified as a closely related homologue of hepatitis C virus (HCV) in the United States, the United Kingdom, and Germany, but not in Asian countries. In this study, we genetically and serologically screened 31 serum samples obtained from Japanese-born domestic horses for EHcV infection and subsequently identified 11 PCR-positive and 7 seropositive serum samples. We determined the full sequence of the EHcV genome, including the 3' untranslated region (UTR), which had previously not been completely revealed. The polyprotein of a Japanese EHcV strain showed approximately 95% homology to those of the reported strains. HCV-like cis-acting RNA elements, including the stem-loop structures of the 3' UTR and kissing-loop interaction were deduced from regions around both UTRs of the EHcV genome. A comparison of the EHcV and HCV core proteins revealed that Ile(190) and Phe(191) of the EHcV core protein could be important for cleavage of the core protein by signal peptide peptidase (SPP) and were replaced with Ala and Leu, respectively, which inhibited intramembrane cleavage of the EHcV core protein. The loss-of-function mutant of SPP abrogated intramembrane cleavage of the EHcV core protein and bound EHcV core protein, suggesting that the EHcV core protein may be cleaved by SPP to become a mature form. The wild-type EHcV core protein, but not the SPP-resistant mutant, was localized on lipid droplets and partially on the lipid raft-like membrane in a manner similar to that of the HCV core protein. These results suggest that EHcV may conserve the genetic and biological properties of HCV. Objective: EHcV, which shows the highest amino acid or nucleotide homology to HCV among hepaciviruses, was previously reported to infect horses from Western, but not Asian, countries. We herein report EHcV infection in Japanese-born horses. In this study, HCV-like RNA secondary structures around both UTRs were predicted by determining the whole-genome sequence of EHcV. Our results also suggest that the EHcV core protein is cleaved by SPP to become a mature form and then is localized on lipid droplets and partially on lipid raft-like membranes in a manner similar to that of the HCV core protein. Hence, EHcV was identified as a closely related homologue of HCV based on its genetic structure as well as its biological properties. A clearer understanding of the epidemiology, genetic structure, and infection mechanism of EHcV will assist in elucidating the evolution of hepaciviruses as well as the development of surrogate models for the study of HCV.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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Publication Date: 2014-09-10 PubMed ID: 25210167PubMed Central: PMC4249100DOI: 10.1128/JVI.02280-14Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates the presence of Equine Hepacivirus (EHcV), previously found only in Western countries in horses, in Japan and further characterizes its genetic and structural similarities with the human Hepatitis C Virus (HCV).

Detection of EHcV in Japanese Horses

  • The study used 31 serum samples from Japanese-born domestic horses, and through genetic and serological screening, discovered 11 PCR-positive and 7 seropositive samples for EHcV.
  • This is the first time EHcV has been found in non-Western countries, thereby making it an international concern.

Genetic Similarities between EHcV and HCV

  • After sequencing the extracted EHcV, the researchers observed a 95% homology with previously reported strains of the virus.
  • Special emphasis was given to the comparison of the core proteins of both viruses( EHcV and HCV), revealing similar RNA secondary structures around UTRs and a conceivable identical cleavage process by signal peptide peptidase (SPP).

Localization of EHcV Core Protein

  • The study also discovers that the core protein of EHcV, post cleavage by SPP, migrates to the lipid droplets and lipid raft-like membranes, akin to the behaviour of HCV core protein.
  • This adds to the biological similarities between the EHcV and HCV adding to the conjecture that EHcV is a very close homologue of HCV.

Implication of Research Findings

  • These results help in understanding the genetic and biological characteristics of EHcV, thereby enhancing our comprehension of Hepacivirus evolution.
  • It also aids in developing surrogate models for studying HCV as they have common properties.
  • Better understanding of EHcV can also assist in the development of potential diagnostic and therapeutic tools for HCV.

Cite This Article

APA
Tanaka T, Kasai H, Yamashita A, Okuyama-Dobashi K, Yasumoto J, Maekawa S, Enomoto N, Okamoto T, Matsuura Y, Morimatsu M, Manabe N, Ochiai K, Yamashita K, Moriishi K. (2014). Hallmarks of hepatitis C virus in equine hepacivirus. J Virol, 88(22), 13352-13366. https://doi.org/10.1128/JVI.02280-14

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 88
Issue: 22
Pages: 13352-13366

Researcher Affiliations

Tanaka, Tomohisa
  • Department of Microbiology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Kasai, Hirotake
  • Department of Microbiology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Yamashita, Atsuya
  • Department of Microbiology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Okuyama-Dobashi, Kaori
  • Department of Microbiology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Yasumoto, Jun
  • Department of Microbiology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Maekawa, Shinya
  • First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Enomoto, Nobuyuki
  • First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Okamoto, Toru
  • Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Matsuura, Yoshiharu
  • Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Morimatsu, Masami
  • Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Manabe, Noboru
  • Animal Resource Science Center, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Kasama, Japan.
Ochiai, Kazuhiko
  • Department of Basic Science, School of Veterinary Nursing and Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo, Japan.
Yamashita, Kazuto
  • Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan.
Moriishi, Kohji
  • Department of Microbiology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan kmoriishi@yamanashi.ac.jp.

MeSH Terms

  • Animals
  • Conserved Sequence
  • Gene Order
  • Genome, Viral
  • Hepacivirus / genetics
  • Hepacivirus / immunology
  • Hepacivirus / isolation & purification
  • Hepatitis C / veterinary
  • Hepatitis C / virology
  • Hepatitis C Antibodies / blood
  • Horse Diseases / virology
  • Horses
  • Japan
  • Molecular Sequence Data
  • RNA, Viral / blood
  • RNA, Viral / genetics
  • Sequence Analysis, DNA
  • Sequence Homology

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