Zika virus and interferon

Zika virus - NIAID Zika virus cannot replicate in mice – unless you knock out the mouse type I interferon with antibodies. As we know, Zika can replicate all too well in humans, but the pathogenesis and cell tropism of this troubling virus is not well understood. This new paper shows that there are important differences in the original African strains of Zika virus and the strains which have spread around the world recently. Understanding these differences might help us explain why this troublesome virus seemingly emerged out of nowhere to cause so much grief.


Zika Virus Antagonizes Type I Interferon Responses during Infection of Human Dendritic Cells. (2017) PLoS Pathog 13(2): e1006164. doi: 10.1371/journal.ppat.1006164
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that, upon congenital infection, can cause severe neonatal birth defects. To better understand the early innate immune response to ZIKV, we compared infection of human dendritic cells (DCs) between a contemporary Puerto Rican isolate and historic isolates from Africa and Asia. Human DCs supported productive replication following infection with the contemporary strain and exhibited donor variability in viral replication, but not viral binding. While contemporary and historic Asian lineage viruses replicated similarly, the African strains displayed more rapid replication kinetics with higher infection magnitude and uniquely induced cell death. Minimal DC activation and antagonism of type I interferon (IFN) translation was observed during ZIKV infection, despite strong induction of IFNB1 transcription and translation of other antiviral effector proteins. Treatment with a RIG-I agonist potently blocked ZIKV replication in human DCs, while type I IFN treatment was significantly less effective. Mechanistically, all ZIKV strains inhibited type I IFN receptor signaling through blockade of STAT1 and STAT2 phosphorylation. Altogether, we found that while ZIKV efficiently evades type I IFN responses during infection of human DCs, RIG-I signaling remains capable of inducing a strong antiviral state.

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