The Interferon (IFN) response is crucial to restrain pathogenic infections. Investigations into flavivirus-host interactions reported that the high virulence is linked to innate immune evasion. Zika Virus (ZIKV) has developed diversified strategies to evade the innate immune system. We report that the viral protein NS2A counteracts the IFN response by strongly suppressing the IFN signaling. NS2A targets transcription factors STAT1 and STAT2, to impede their nuclear localization, thereby suppressing the transcription of ISRE promoter and IFN-stimulated genes. We found that NS2A promotes degradation of STAT1 and STAT2. Treatment of NS2A transfected cells with MG132 restores the levels of both transcription factors, suggesting the involvement of the proteasome system. Given the impact that the IFN antagonism has on flavivirus virulence, the knowledge gained by characterizing the mechanism through which ZIKV evades the IFN response paves the ground for new strategies to attenuate the pathogenesis and to develop countermeasures against effective pharmacological targets.

Zika virus NS2A inhibits interferon signaling by degradation of STAT1 and STAT2

Fanunza, Elisa
Primo
;
Quartu, Marina;Grandi, Nicole;Ermellino, Laura;Milia, Jessica;Corona, Angela;Capobianchi, Maria Rosaria;Ippolito, Giuseppe;Tramontano, Enzo
Ultimo
2021-01-01

Abstract

The Interferon (IFN) response is crucial to restrain pathogenic infections. Investigations into flavivirus-host interactions reported that the high virulence is linked to innate immune evasion. Zika Virus (ZIKV) has developed diversified strategies to evade the innate immune system. We report that the viral protein NS2A counteracts the IFN response by strongly suppressing the IFN signaling. NS2A targets transcription factors STAT1 and STAT2, to impede their nuclear localization, thereby suppressing the transcription of ISRE promoter and IFN-stimulated genes. We found that NS2A promotes degradation of STAT1 and STAT2. Treatment of NS2A transfected cells with MG132 restores the levels of both transcription factors, suggesting the involvement of the proteasome system. Given the impact that the IFN antagonism has on flavivirus virulence, the knowledge gained by characterizing the mechanism through which ZIKV evades the IFN response paves the ground for new strategies to attenuate the pathogenesis and to develop countermeasures against effective pharmacological targets.
2021
Zika virus; Ns2a; interferon; Ifn signaling; Ifn evasion; stat1; stat2; degradation; phosphorylation
File in questo prodotto:
File Dimensione Formato  
2021 Zika virus NS2A inhibits interferon signaling by degradation of STAT1 and STAT2.pdf

accesso aperto

Tipologia: versione editoriale
Dimensione 4.88 MB
Formato Adobe PDF
4.88 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/316823
Citazioni
  • ???jsp.display-item.citation.pmc??? 11
  • Scopus 21
  • ???jsp.display-item.citation.isi??? 22
social impact