Although dendritic cells (DCs) are among the human cell population best equipped for cell-intrinsic antiviral immune defense, they seem highly susceptible to infection with Zika Virus (ZIKV). Using highly-purified mDC isolated from individuals with naturally-acquired acute infection, we here show that ZIKV induces profound perturbations of transcriptional signatures relative to uninfected patients. Interestingly, we noted a remarkable downregulation of antiviral Interferon-stimulated genes and innate immune sensors, suggesting that ZIKV can actively suppress Interferon-dependent immune responses. In contrast, several host factors known to support ZIKV infection were strongly upregulated during natural ZIKV infection; these transcripts included AXL, the main entry receptor for ZIKV, SOCS3, a negative regulator of ISG expression, and IDO-1, a recognized inducer of regulatory T cell responses. Thus, during in vivo infection, ZIKV can transform the transcriptome of dendritic cells in favor of the virus to render these cells highly conducive to ZIKV infection. SOURCE: Xu,G,Yu (XYU@mgh.harvard.edu) - Yu's Group Ragon Institute of MGH, MIT and Harvard

Pluto Bioinformatics

GSE101878: Transcriptional changes during naturally-acquired ZIKA Virus infection render dendritic cells highly conducive to viral replication