Varicella Viruses Inhibit Interferon-Stimulated JAK-STAT Signaling through Multiple Mechanisms

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In this manuscript we demonstrate that the immediate early protein ORF63 encoded by varicella zoster virus (VZV) and simian varicella virus (SVV) interferes with interferon type I-mediated activation of JAK-STAT signaling and thereby inhibits the expression of interferon stimulated genes. ORF63 blocks this pathway by degrading IRF9, which plays a central role in JAK-STAT signaling. In addition, both viruses code for immune evasion mechanisms affecting the JAK-STAT pathway upstream of IRF9, which results in the inhibition of STAT2 phosphorylation. By fusing a degradation domain derived from dihydrofolate reductase (DHFR) to ORF63 we further demonstrate that this protein is essential for SVV growth and gene expression, indicating that ORF63 also affects IFN-signaling indirectly by regulating the expression of other immune evasion genes.

Vyšlo v časopise: Varicella Viruses Inhibit Interferon-Stimulated JAK-STAT Signaling through Multiple Mechanisms. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004901
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004901

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