Transcriptional Changes during Naturally Acquired Zika Virus Infection Render Dendritic Cells Highly Conducive to Viral Replication

Publication date: 19 December 2017
Source:Cell Reports, Volume 21, Issue 12
Author(s): Xiaoming Sun, Stephane Hua, Hsiao-Rong Chen, Zhengyu Ouyang, Kevin Einkauf, Samantha Tse, Kevin Ard, Andrea Ciaranello, Sigal Yawetz, Paul Sax, Eric S. Rosenberg, Mathias Lichterfeld, Xu G. Yu
Although dendritic cells are among the human cell population best equipped for cell-intrinsic antiviral immune defense, they seem highly susceptible to infection with the 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.

Graphical abstract

Teaser

Sun et al. find distinct transcriptional signatures in myeloid dendritic cells isolated from individuals with naturally acquired Zika Virus infection. These data indicate that Zika virus can reprogram dendritic cells to increase their susceptibility to further ZIKV infection.


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