1887

Journal of General Virology header logo

Volume 104, Issue 10

The parapoxvirus Orf virus inhibits dsDNA-mediated type I IFN expression via STING-dependent and STING-independent signalling pathways No Access

Abstract

Type I interferons (IFNs) are critical in the host defence against viruses. They induce hundreds of interferon-stimulated genes (ISGs) many of which have an antiviral role. Poxviruses induce IFNs via their pathogen-associated molecular patterns, in particular, their genomic DNA. In a majority of cell types, dsDNA is detected by a range of cytoplasmic DNA sensors that mediate type I IFN expression via stimulator of interferon genes (STING). Orf virus (ORFV) induces cutaneous pustular skin lesions and is the type species of the Parapoxvirus genus within the family. The aim of this study was to investigate whether ORFV modulates dsDNA-induced type I IFN expression via STING-dependent signalling pathways in human dermal fibroblasts (hNDF) and THP-1 cells. We showed that ORFV infection of these cell types treated with poly(dA:dT) resulted in strong inhibition of expression of IFN-β. In hNDFs, we showed using siRNA knock-down that STING was essential for type I IFN induction. IFN-β expression was further reduced when both STING and RIG-I were knocked down. In addition, HEK293 cells that do not express STING or Toll-like receptors also produce IFN-β following stimulation with poly(dA:dT). The 5′ triphosphate dsRNA produced by RNA polymerase III specifically results in the induction of type I IFNs through the RIG-I receptor. We showed that ORFV infection resulted in strong inhibition of IFN-β expression in HEK293 cells stimulated with poly(dA:dT). Overall, this study shows that ORFV potently counteracts the STING-dependent and STING-independent IFN response by antagonizing dsDNA-activated IFN signalling pathways.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): DNA sensors , immune modulation , interferon-beta , ORFV , poxvirus and STING
Funding
This study was supported by the:
  • Health Research Council of New Zealand (Award 13/774)
    • Principle Award Recipient: StephenBruce Fleming
  • Health Research Council of New Zealand (Award 13/774)
    • Principle Award Recipient: AndrewA Mercer
© 2023 The Authors
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/content/journal/jgv/10.1099/jgv.0.001912
2023-10-26
2024-05-20
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The parapoxvirus Orf virus inhibits dsDNA-mediated type I IFN expression via STING-dependent and STING-independent signalling pathways
J. Gen. Virol. 104, 001912 (2023); https://doi.org/10.1099/jgv.0.001912
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