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Cell Rep. 2017 Dec 19;21(12):3471-3482. doi: 10.1016/j.celrep.2017.11.087.

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

Author information

1
Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Boston, MA.
2
Infectious Disease Division, Massachusetts General Hospital, Boston, MA.
3
Infectious Disease Division, Brigham and Women's Hospital, Boston, MA.
4
Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Boston, MA; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA.
5
Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Boston, MA; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA. Electronic address: xyu@mgh.harvard.edu.

Abstract

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.

KEYWORDS:

AXL; IDO-1; RNA-seq; SOCS3; Zika virus; acute infection; dendritic cells; flavivirus; interferon stimulated genes

PMID:
29262327
PMCID:
PMC5751936
DOI:
10.1016/j.celrep.2017.11.087
[Indexed for MEDLINE]
Free PMC Article

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