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

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
Inglese
12
1
1580
1596
17
https://www.tandfonline.com/doi/full/10.1080/21505594.2021.1935613?scroll=top&needAccess=true
Esperti anonimi
internazionale
scientifica
Zika virus; Ns2a; interferon; Ifn signaling; Ifn evasion; stat1; stat2; degradation; phosphorylation
no
Fanunza, Elisa; Carletti, Fabrizio; Quartu, Marina; Grandi, Nicole; Ermellino, Laura; Milia, Jessica; Corona, Angela; Capobianchi, Maria Rosaria; Ippolito, Giuseppe; Tramontano, Enzo
1.1 Articolo in rivista
info:eu-repo/semantics/article
1 Contributo su Rivista::1.1 Articolo in rivista
262
10
open
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