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Home / Equine Research Bank / PLoS One / Canine hepacivirus NS3 serine protease can cleave the human ...
PloS one2012; 7(8); e42481; doi: 10.1371/journal.pone.0042481

Canine hepacivirus NS3 serine protease can cleave the human adaptor proteins MAVS and TRIF.

Abstract: Canine hepacivirus (CHV) was recently identified in domestic dogs and horses. The finding that CHV is genetically the virus most closely related to hepatitis C virus (HCV) has raised the question of whether HCV might have evolved as the result of close contact between dogs and/or horses and humans. The aim of this study was to investigate whether the NS3/4A serine protease of CHV specifically cleaves human mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF). The proteolytic activity of CHV NS3/4A was evaluated using a bacteriophage lambda genetic screen. Human MAVS- and TRIF-specific cleavage sites were engineered into the lambda cI repressor. Upon infection of Escherichia coli cells coexpressing these repressors and a CHV NS3/4A construct, lambda phage replicated up to 2000-fold more efficiently than in cells expressing a CHV protease variant carrying the inactivating substitution S139A. Comparable results were obtained when several HCV NS3/4A constructs of genotype 1b were assayed. This indicates that CHV can disrupt the human innate antiviral defense signaling pathway and suggests a possible evolutionary relationship between CHV and HCV.
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Publication Date: 2012-08-01 PubMed ID: 22870331PubMed Central: PMC3411667DOI: 10.1371/journal.pone.0042481Google 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 research article aims to explore whether the NS3/4A serine protease of Canine Hepacivirus (CHV) can specifically cleave human mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF).

Research Background

  • The research investigates the interaction between a canine virus, Canine Hepacivirus (CHV), and specific human adaptor proteins— mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF).
  • This study stems from the discovery that CHV is the virus most closely related to the hepatitis C virus (HCV) in humans. There is speculation about an evolutionary relationship between the viruses possibly due to contact between dogs/horses and humans.

Objective and Methodology

  • The aim of the study was to examine whether the NS3/4A serine protease of CHV could cleave— or split— these human proteins, suggesting a potential interaction or compatibility between CHV and human cells.
  • The researchers examined the proteolytic activity (the ability to break down proteins by enzymatic action) of the CHV NS3/4A through a bacteriophage lambda genetic screen.
  • The method involved engineering human MAVS- and TRIF-specific cleavage sites into the lambda cI repressor.
  • Escherichia coli cells coexpressing these repressors and a CHV NS3/4A construct were infected. On infection, the lambda phage showed significantly higher replicative efficiency.

Key Findings

  • It was observed that lambda phage replicated up to 2000-fold more efficiently in cells expressing a CHV NS3/4A construct compared to those expressing a CHV protease variant with an inactivating substitution (S139A).
  • The researchers obtained similar results when assaying several HCV NS3/4A constructs, indicating that both types of virus can interrupt the human innate antiviral defense signaling pathway.

Conclusion and Implications

  • The research suggests a possible evolutionary relationship between CHV and HCV, as both were found capable of cleaving human MAVS and TRIF.
  • These findings might be important for understanding the evolution and cross-species transmission of these viruses, and could provide insights with implications for human health and disease management.

Cite This Article

APA
Parera M, Martrus G, Franco S, Clotet B, Martinez MA. (2012). Canine hepacivirus NS3 serine protease can cleave the human adaptor proteins MAVS and TRIF. PLoS One, 7(8), e42481. https://doi.org/10.1371/journal.pone.0042481

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 7
Issue: 8
Pages: e42481
PII: e42481

Researcher Affiliations

Parera, Mariona
  • Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), Badalona, Spain.
Martrus, Gloria
    Franco, Sandra
      Clotet, Bonaventura
        Martinez, Miguel Angel

          MeSH Terms

          • Adaptor Proteins, Signal Transducing / chemistry
          • Adaptor Proteins, Signal Transducing / genetics
          • Adaptor Proteins, Signal Transducing / immunology
          • Adaptor Proteins, Signal Transducing / metabolism
          • Adaptor Proteins, Vesicular Transport / chemistry
          • Adaptor Proteins, Vesicular Transport / genetics
          • Adaptor Proteins, Vesicular Transport / immunology
          • Adaptor Proteins, Vesicular Transport / metabolism
          • Adenoviruses, Canine / enzymology
          • Adenoviruses, Canine / genetics
          • Adenoviruses, Canine / immunology
          • Animals
          • Dogs
          • Hepacivirus / enzymology
          • Hepacivirus / genetics
          • Hepacivirus / immunology
          • Hepacivirus / metabolism
          • Humans
          • Immunity, Innate / genetics
          • Proteolysis
          • Recombinant Proteins / chemistry
          • Recombinant Proteins / genetics
          • Recombinant Proteins / immunology
          • Recombinant Proteins / metabolism
          • Serine Endopeptidases / chemistry
          • Serine Endopeptidases / genetics
          • Serine Endopeptidases / immunology
          • Serine Endopeptidases / metabolism
          • Signal Transduction / genetics
          • Signal Transduction / immunology
          • Viral Nonstructural Proteins / chemistry
          • Viral Nonstructural Proteins / genetics
          • Viral Nonstructural Proteins / immunology
          • Viral Nonstructural Proteins / metabolism

          Conflict of Interest Statement

          The authors have declared that no competing interests exist.

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