Summary
Although dendritic cells 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 myeloid
dendritic cells isolated from individuals with naturally-acquired acute
infection, we here show that ZIKV induces profound perturbations of
transcriptional signatures relative to healthy donors. 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.