Conserved Antagonization of Type I Interferon Signaling by Arterivirus GP5 Proteins.
Abstract: can establish persistent infections in animals such as equids, pigs, nonhuman primates, rodents, and possums. Some can even cause overt and severe diseases such as Equine Arteritis in horses and Porcine Reproductive and Respiratory Syndrome in pigs, leading to huge economic losses. have evolved viral proteins to antagonize the host cell's innate immune responses by inhibiting type I interferon (IFN) signaling, assisting viral evasion and persistent infection. So far, the role of the glycoprotein 5 (GP5) protein in IFN signaling inhibition remains unclear. Here, we investigated the inhibitory activity of 47 GP5 proteins derived from various hosts. We demonstrated that all GP5 proteins showed conserved activity for antagonizing TIR-domain-containing adapter proteins inducing interferon-β (TRIF)-mediated IFN-β signaling through TRIF degradation. In addition, GP5 proteins showed a conserved inhibitory activity against IFN-β signaling, induced by either pig or human TRIF. Furthermore, certain GP5 proteins could inhibit the induction of IFN-stimulated genes. These findings highlight the role of GP5 proteins in supporting persistent infection.
Publication Date: 2024-08-01 PubMed ID: 39205214PubMed Central: PMC11358952DOI: 10.3390/v16081240Google Scholar: Lookup
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Summary
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The research article reveals that all Arterivirus GP5 proteins have conserved activity in antagonizing type I interferon signaling, showing that these proteins aid in persistent viral infection.
Background
- The virus known as Arterivirus can cause persistent infection in a diverse group of animals, leading to diseases like Equine Arteritis in horses and Porcine Reproductive and Respiratory Syndrome in pigs.
- These diseases can significantly impact agricultural economies due to loss of livestock.
- Arterivirus has developed ways to hinder the host cell’s innate immune responses, particularly by inhibiting type I interferon (IFN) signaling, thus aiding viral evasion and persistent infection.
- So far, the role of Arterivirus glycoprotein 5 (GP5) protein in this inhibition process remained unclear, initiating the significance of the study.
Methodology
- The team investigated the inhibitory activity in 47 Arterivirus GP5 proteins taken from a wide range of hosts.
- The research study used TRIF, or TIR-domain-containing adapter proteins inducing interferon-β, for testing the GP5 proteins’ antagonistic activity.
- Both pig and human TRIF were used to gauge the inhibitory activity against IFN-β signaling by the GP5 proteins.
Findings
- The study found that all of the 47 GP5 proteins from Arterivirus demonstrated conserved activity in antagonizing TRIF-mediated IFN-β signaling due to TRIF degradation.
- This antagonistic activity is universally inhibitory against IFN-β signaling, as confirmed by both pig and human TRIF inducements.
- Further, it was discovered that some GP5 proteins could inhibit the induction of interferon-stimulated genes, highlighting GP5 proteins’ role in maintaining persistent viral infections.
Implications
- This research provides valuable insights into how Arterivirus remains persistent in hosts by employing GP5 proteins to weaken the immune response.
- The findings may potentially lead to the development of novel antiviral strategies by targeting this GP5-mediated interference of immune signaling.
Cite This Article
APA
Ringo RS, Choonnasard A, Okabayashi T, Saito A.
(2024).
Conserved Antagonization of Type I Interferon Signaling by Arterivirus GP5 Proteins.
Viruses, 16(8), 1240.
https://doi.org/10.3390/v16081240 Publication
Researcher Affiliations
- Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan.
- Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
- Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan.
- Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
- Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan.
- Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
- Center for Animal Disease Control, University of Miyazaki, Miyazaki 889-2192, Japan.
- Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan.
- Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
- Center for Animal Disease Control, University of Miyazaki, Miyazaki 889-2192, Japan.
MeSH Terms
- Animals
- Signal Transduction
- Arterivirus / genetics
- Arterivirus / metabolism
- Humans
- Swine
- Interferon Type I / metabolism
- Arterivirus Infections / veterinary
- Arterivirus Infections / virology
- Arterivirus Infections / immunology
- Interferon-beta / metabolism
- Interferon-beta / genetics
- Immunity, Innate
- Viral Proteins / metabolism
- Viral Proteins / genetics
- HEK293 Cells
Grant Funding
- JP24fk0410047, JP24fk0410056, and JP24fk0410058, JP22fk0108511, JP22fk0108506 / Japan Agency for Medical Research and Development (AMED)
- JP24K09227, JPJSBP120245706, JP22H02500, JP21H02361, JP23K20041 / JSPS
- n/a / G-7 Grant
- R5 KEN77, R6 KEN119 / Ito Foundation Research Grant
Conflict of Interest Statement
The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
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