AI Article Synopsis
- * ZIKV NS4B was characterized from a strain linked to the 2016 outbreak and found to have similarities with the NS4B protein of Dengue virus 2, suggesting a common mechanism for immune evasion.
- * Findings revealed that ZIKV NS4B significantly inhibits the IFN signaling pathway by preventing the activation and transport of key proteins (STAT1 and STAT2), thereby dampening the immune response.
Article Abstract
The evasion of the Interferon response has important implications in Zika virus (ZIKV) disease. Mutations in ZIKV viral protein NS4B, associated with modulation of the interferon (IFN) system, have been linked to increased pathogenicity in animal models. In this study, we unravel ZIKV NS4B as antagonist of the IFN signaling cascade. Firstly, we reported the genomic characterization of NS4B isolated from a strain of the 2016 outbreak, ZIKV Brazil/2016/INMI1, and we predicted its membrane topology. Secondly, we analyzed its phylogenetic correlation with other flaviviruses, finding a high similarity with dengue virus 2 (DEN2) strains; in particular, the highest conservation was found when NS4B was aligned with the IFN inhibitory domain of DEN2 NS4B. Hence, we asked whether ZIKV NS4B was also able to inhibit the IFN signaling cascade, as reported for DEN2 NS4B. Our results showed that ZIKV NS4B was able to strongly inhibit the IFN stimulated response element and the IFN-γ-activated site transcription, blocking IFN-I/-II responses. mRNA expression levels of the IFN stimulated genes and were also strongly reduced in presence of NS4B. We found that the viral protein was acting by suppressing the STAT1 phosphorylation and consequently blocking the nuclear transport of both STAT1 and STAT2.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8705506 | PMC |
| http://dx.doi.org/10.3390/v13122448 | DOI Listing |
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