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

Cell Reports. 2017;21(12):3471-3482

 

Journal Homepage

Journal Title: Cell Reports

ISSN: 2211-1247 (Online)

Publisher: Elsevier

LCC Subject Category: Science: Biology (General)

Country of publisher: Netherlands

Language of fulltext: English

Full-text formats available: PDF, HTML

 

AUTHORS


Xiaoming Sun (Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Boston, MA)

Stephane Hua (Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Boston, MA)

Hsiao-Rong Chen (Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Boston, MA)

Zhengyu Ouyang (Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Boston, MA)

Kevin Einkauf (Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Boston, MA)

Samantha Tse (Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Boston, MA)

Kevin Ard (Infectious Disease Division, Massachusetts General Hospital, Boston, MA)

Andrea Ciaranello (Infectious Disease Division, Massachusetts General Hospital, Boston, MA)

Sigal Yawetz (Infectious Disease Division, Brigham and Women’s Hospital, Boston, MA)

Paul Sax (Infectious Disease Division, Brigham and Women’s Hospital, Boston, MA)

Eric S. Rosenberg (Infectious Disease Division, Massachusetts General Hospital, Boston, MA)

Mathias Lichterfeld (Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Boston, MA; Infectious Disease Division, Brigham and Women’s Hospital, Boston, MA)

Xu G. Yu (Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Boston, MA; Infectious Disease Division, Brigham and Women’s Hospital, Boston, MA; Corresponding author)

EDITORIAL INFORMATION

Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 31 weeks

 

Abstract | Full Text

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 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. : 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. Keywords: Zika virus, flavivirus, interferon stimulated genes, dendritic cells, acute infection, RNA-seq, SOCS3, IDO-1, AXL