1. IL-1β/TNF-α/IL-6 inflammatory cytokines promote STAT1-dependent induction of CH25H in Zika virus-infected human macrophages.
- Author
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Magoro T, Dandekar A, Jennelle LT, Bajaj R, Lipkowitz G, Angelucci AR, Bessong PO, and Hahn YS
- Subjects
- Antiviral Agents chemistry, Antiviral Agents metabolism, Cytokines genetics, DNA-Binding Proteins chemistry, DNA-Binding Proteins genetics, Gene Expression Regulation, Enzymologic, Humans, Inflammation enzymology, Inflammation genetics, Inflammation virology, Interferon Type I genetics, Interleukin-1beta genetics, Interleukin-6 genetics, Macrophages virology, Steroid Hydroxylases chemistry, Toll-Like Receptors genetics, Tumor Necrosis Factor-alpha genetics, Virus Replication genetics, Zika Virus pathogenicity, Zika Virus Infection enzymology, Zika Virus Infection virology, Activating Transcription Factor 3 genetics, STAT1 Transcription Factor genetics, Steroid Hydroxylases genetics, Zika Virus genetics, Zika Virus Infection genetics
- Abstract
Zika virus (ZIKV)
3 is an enveloped, single-stranded, positive-sense RNA virus of the Flaviviridae family that has emerged as a public health threat because of its global transmission and link to microcephaly. Currently there is no vaccine for this virus. Conversion of cholesterol to 25-hydroxycholesterol by cholesterol 25-hydroxylase (CH25H) has been shown to have broad antiviral properties. However, the molecular basis of induction of CH25H in humans is not known. Elucidation of signaling and transcriptional events for induction of CH25H expression is critical for designing therapeutic antiviral agents. In this study, we show that CH25H is induced by ZIKV infection or Toll-like receptor stimulation. Interestingly, CH25H is induced by pro-inflammatory cytokines, including IL-1β, tumor necrosis factor α, and IL-6, and this induction depends on the STAT1 transcription factor. Additionally, we observed that cAMP-dependent transcription factor (ATF3) weakly binds to the CH25H promoter, suggesting cooperation with STAT1. However, ZIKV-induced CH25H was independent of type I interferon. These findings provide important information for understanding how the Zika virus induces innate inflammatory responses and promotes the expression of anti-viral CH25H protein., (© 2019 Magoro et al.)- Published
- 2019
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