Zika Virus Antagonizes Type I Interferon Responses during Infection of Human Dendritic Cells

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that is causally linked to severe neonatal birth defects, including microcephaly, and is associated with Guillain-Barre syndrome in adults. Dendritic cells (DCs) are an important cell type during infection by multiple mosquito-borne flavivir...

Full description

Saved in:
Bibliographic Details
Published in:PLoS pathogens 2017-02, Vol.13 (2), p.e1006164
Main Authors: Bowen, James R, Quicke, Kendra M, Maddur, Mohan S, O'Neal, Justin T, McDonald, Circe E, Fedorova, Nadia B, Puri, Vinita, Shabman, Reed S, Pulendran, Bali, Suthar, Mehul S
Format: Article
Language:English
Subjects:
Apoptosis
Biology and Life Sciences
Birth defects
Blotting, Western
Cytokines
DEAD Box Protein 58 - immunology
Dendritic cells
Dendritic Cells - immunology
Dendritic Cells - virology
Dosage and administration
Flaviviridae
Flavivirus
Flow Cytometry
Funding
Guillain-Barre syndrome
Humans
Immune Evasion - immunology
Infections
Infectious diseases
Interferon
Interferon Type I - immunology
Laboratories
Medicine
Medicine and Health Sciences
Mosquitoes
Pediatrics
Phosphorylation
Polymerase Chain Reaction
Prevention
Proteins
Receptors, Immunologic
Research and Analysis Methods
Risk factors
West Nile virus
Zika virus
Zika Virus - immunology
Zika Virus Infection - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that is causally linked to severe neonatal birth defects, including microcephaly, and is associated with Guillain-Barre syndrome in adults. Dendritic cells (DCs) are an important cell type during infection by multiple mosquito-borne flaviviruses, including dengue virus, West Nile virus, Japanese encephalitis virus, and yellow fever virus. Despite this, the interplay between ZIKV and DCs remains poorly defined. Here, we found human DCs supported productive infection by a contemporary Puerto Rican isolate with considerable variability in viral replication, but not viral binding, between DCs from different donors. Historic isolates from Africa and Asia also infected DCs with distinct viral replication kinetics between strains. African lineage viruses displayed more rapid replication kinetics and infection magnitude as compared to Asian lineage viruses, and uniquely induced cell death. Infection of DCs with both contemporary and historic ZIKV isolates led to minimal up-regulation of T cell co-stimulatory and MHC molecules, along with limited secretion of inflammatory cytokines. Inhibition of type I interferon (IFN) protein translation was observed during ZIKV infection, despite strong induction at the RNA transcript level and up-regulation of other host antiviral proteins. Treatment of human DCs with RIG-I agonist potently restricted ZIKV replication, while type I IFN had only modest effects. Mechanistically, we found all strains of ZIKV antagonized type I IFN-mediated phosphorylation of STAT1 and STAT2. Combined, our findings show that ZIKV subverts DC immunogenicity during infection, in part through evasion of type I IFN responses, but that the RLR signaling pathway is still capable of inducing an antiviral state, and therefore may serve as an antiviral therapeutic target.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1006164