Structural modeling and analysis of dengue-mediated inhibition of interferon signaling pathway

Aslam, Baber; Ahmad, Jamil; Ali, Amjad; Paracha, Rehan Zafar; Tareen, Samar; Khusro, Shah; Ahmad, Tahir; Muhammad, Syed Aun; Niazi, Umar; Azevedo, Rodolfo

doi:10.4238/2015.april.28.4

Cited by 7 publications

(5 citation statements)

References 72 publications

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“…Disruption of these interactions abrogated NS5-mediated hSTAT2 degradation, interferon suppression, and viral infection. These results are also in agreement with previous demonstration that the difference in NS5-mediated binding and degradation between hSTAT2 (NS5-sensitive) and mSTAT2 (NS5-resistant) maps largely to the coiled-coil domain [ 85 ]. Very recently, the coiled-coil domain was also shown to be necessary and sufficient for STAT2 degradation by ZIKV NS5 [ 86 ], suggesting conservation of this mechanism between these two flavivurses.…”

Section: Stat2 Degradation By the Ubiquitin–proteasome System (Ups)supporting

confidence: 93%

Mechanisms of Viral Degradation of Cellular Signal Transducer and Activator of Transcription 2

Barik¹

2022

IJMS

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Virus infection of eukaryotes triggers cellular innate immune response, a major arm of which is the type I interferon (IFN) family of cytokines. Binding of IFN to cell surface receptors triggers a signaling cascade in which the signal transducer and activator of transcription 2 (STAT2) plays a key role, ultimately leading to an antiviral state of the cell. In retaliation, many viruses counteract the immune response, often by the destruction and/or inactivation of STAT2, promoted by specific viral proteins that do not possess protease activities of their own. This review offers a summary of viral mechanisms of STAT2 subversion with emphasis on degradation. Some viruses also destroy STAT1, another major member of the STAT family, but most viruses are selective in targeting either STAT2 or STAT1. Interestingly, degradation of STAT2 by a few viruses requires the presence of both STAT proteins. Available evidence suggests a mechanism in which multiple sites and domains of STAT2 are required for engagement and degradation by a multi-subunit degradative complex, comprising viral and cellular proteins, including the ubiquitin–proteasomal system. However, the exact molecular nature of this complex and the alternative degradation mechanisms remain largely unknown, as critically presented here with prospective directions of future study.

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Section: Stat2 Degradation By the Ubiquitin–proteasome System (Ups)supporting

confidence: 93%

Mechanisms of Viral Degradation of Cellular Signal Transducer and Activator of Transcription 2

Barik¹

2022

IJMS

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“…These factors encompass inhibitors of dsRNA sensors 171,172 and their transducers 173 , dsDNA sensors 174 and their transducers [175][176][177][178] and the transcription factors executing the cellular response to foreign nucleic acids, including IRF3 and IRF7 (refs. 176,177,[179][180][181][182] ). Along similar lines, cancer cells harness strategies to limit nucleic-acid-driven innate immune signaling in support of immunoevasion.…”

Section: Subversion Of Icd By Viruses and Cancer Cellsmentioning

confidence: 99%

Immunogenic cell stress and death

et al. 2022

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“…Many researchers had found that NSs of different viruses played important role in blocking interferon-mediated antiviral effect. One report found that non-structure protein 5 (NS5) of Dengue virus (DENV) interacted with STAT2 to block IFN signaling pathway[ 16 ]. Another research claimed that NS5A protein of Hepatitis C Virus (HCV) could disrupt STAT1 phosphorylation and suppressed Type I interferon signaling[ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Severe fever with thrombocytopenia syndrome virus inhibits exogenous Type I IFN signaling pathway through its NSs in vitro

Chen

Yé

et al. 2017

PLoS ONE

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Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus (SFTS virus, SFTSV). At present there is still no specific antiviral treatment for SFTSV; To understand which cells support SFTSV life cycle and whether SFTSV infection activates host innate immunity, four different cell lines (Vero, Hela, Huh7.5.1, and Huh7.0) were infected with SFTSV. Intracellular/extracellular viral RNA and expression of IFNα, and IFNß were detected by real-time RT- PCR following infection. To confirm the role of non-structural protein (NSs) of SFTSV in exogenous IFNα-induced Jak/STAT signaling, p-STAT1 (Western Blot), ISRE activity (Luciferase assay) and ISG expression (real-time PCR) were examined following IFNα stimulation in the presence or absence of over-expression of NSs in Hela cells. Our study showed that all the four cell lines supported SFTSV life cycle and SFTSV activated host innate immunity to produce type I IFNs in Hela cells but not in Huh7.0, Huh7.5.1 or Vero cells. NSs inhibited exogenous IFNα-induced Jak/STAT signaling as shown by decreased p-STAT1 level, suppressed ISRE activity and down-regulated ISG expression. Suppression of the exogenous Type I IFN-induced Jak/STAT signaling by NSs might be one of the mechanisms of SFTSV to evade host immune surveillance.

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Structural modeling and analysis of dengue-mediated inhibition of interferon signaling pathway

Cited by 7 publications

References 72 publications

Mechanisms of Viral Degradation of Cellular Signal Transducer and Activator of Transcription 2

Mechanisms of Viral Degradation of Cellular Signal Transducer and Activator of Transcription 2

Immunogenic cell stress and death

Severe fever with thrombocytopenia syndrome virus inhibits exogenous Type I IFN signaling pathway through its NSs in vitro

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