Zika virus is an emerging mosquito‐borne pathogen that is associated with Guillain–Barré syndrome in adults and microcephaly and other neurological defects in newborns. Despite being declared an international emergency by the World Health Organization, comparatively little is known about its biology. Here, we investigate the strategies employed by the virus to suppress the host antiviral response. We observe that once established, Zika virus infection is impervious to interferon treatment suggesting that the virus deploys effective countermeasures to host cell defences. This is confirmed by experiments showing that Zika virus infection impairs the induction of type‐I interferon as well as downstream interferon‐stimulated genes. Multiple viral proteins affect these processes. Virus‐mediated degradation of STAT2 acts to reduce type‐I and type‐III interferon‐mediated signaling. Further, the NS5 of Zika virus binds to STAT2, and its expression is correlated with STAT2 degradation by the proteasome. Together, our findings provide key insights into how Zika virus blocks cellular defense systems. This in turn is important for understanding pathogenesis and may aid in designing antiviral therapies.
Zika virus (ZIKV) is a mosquito‐borne pathogen that causes Guillain–Barré syndrome in adults and microcephaly in newborns. This report shows that ZIKV infection inhibits the induction of type‐I interferons by downregulating IRF3 and antiviral NF‐κB‐mediated signaling and targets STAT2 for proteasomal degradation.
ZIKV NS1, NS4A, and NS5 interfere with the induction of type‐I interferon.
ZIKV infection inhibits type‐I interferon signaling.
ZIKV infection results in depletion of STAT2 in human cells.
ZIKV NS5 interacts with STAT2 and induces proteasomal degradation of the protein.
EMBO Reports (2016) 17: 1766–1775
- Received April 27, 2016.
- Revision received September 13, 2016.
- Accepted September 22, 2016.
- © 2016 The Authors
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