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

Autor: Elisa Fanunza, Fabrizio Carletti, Marina Quartu, Nicole Grandi, Laura Ermellino, Jessica Milia, Angela Corona, Maria Rosaria Capobianchi, Giuseppe Ippolito, Enzo Tramontano
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Virulence, Vol 12, Iss 1, Pp 1580-1596 (2021)
Druh dokumentu: article
ISSN: 2150-5594
2150-5608
21505594
DOI: 10.1080/21505594.2021.1935613
Popis: 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.
Databáze: Directory of Open Access Journals
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