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Abstract

Phleboviruses (order , family ) are globally emerging arboviruses with a wide spectrum of virulence. Sandfly fever Sicilian virus (SFSV) is one of the most ubiquitous members of the genus and associated with a self-limited, incapacitating febrile disease in travellers and military troops. The phleboviral NSs protein is an established virulence factor, acting as antagonist of the antiviral interferon (IFN) system. Consistently, we previously reported that SFSV NSs targets the induction of IFN mRNA synthesis by specifically binding to the DNA-binding domain of the IFN transcription factor IRF3. Here, we further characterized the effect of SFSV and its NSs towards IFN induction, and evaluated its potential to affect the downstream IFN-stimulated signalling and the subsequent transactivation of antiviral interferon-stimulated genes (ISGs). We found that SFSV dampened, but did not entirely abolish type I and type III IFN induction. Furthermore, SFSV NSs did not affect IFN signalling, resulting in substantial ISG expression in infected cells. Hence, although SFSV targets IRF3 to reduce IFN induction, it is not capable of entirely disarming the IFN system in the presence of high basal IRF3 and/or IRF7 levels, and we speculate that this significantly contributes to its low level of virulence.

Funding
This study was supported by the:
  • swedish research council (Award 2018-05766)
    • Principle Award Recipient: FriedemannWeber
  • bundesministerium für bildung und forschung (Award Infect-ERA, grant “ESCential”)
    • Principle Award Recipient: FriedemannWeber
  • deutsche forschungsgemeinschaft (Award 197785619–SFB 1021)
    • Principle Award Recipient: FriedemannWeber
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2021-11-02
2024-12-07
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