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

作者：J. Richard Bowen, Kendra M. Quicke, Mohan S. Maddur, Justin T. O’Neal, Circe E. McDonald, Nadia Fedorova, Vinita Puri, Reed S. Shabman, Bali Pulendran, Mehul S. Suthar · 发表于：PLoS Pathogens · 年份：2017 · DOI：10.1371/journal.ppat.1006164 · 被引用次数：274 · 研究领域：Mosquito-borne diseases and control、Viral Infections and Vectors、Malaria Research and Control

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...