RRC ID 53205
著者 Liu Y, Gordesky-Gold B, Leney-Greene M, Weinbren NL, Tudor M, Cherry S.
タイトル Inflammation-Induced, STING-Dependent Autophagy Restricts Zika Virus Infection in the Drosophila Brain.
ジャーナル Cell Host Microbe
Abstract The emerging arthropod-borne flavivirus Zika virus (ZIKV) is associated with neurological complications. Innate immunity is essential for the control of virus infection, but the innate immune mechanisms that impact viral infection of neurons remain poorly defined. Using the genetically tractable Drosophila system, we show that ZIKV infection of the adult fly brain leads to NF-kB-dependent inflammatory signaling, which serves to limit infection. ZIKV-dependent NF-kB activation induces the expression of Drosophila stimulator of interferon genes (dSTING) in the brain. dSTING protects against ZIKV by inducing autophagy in the brain. Loss of autophagy leads to increased ZIKV infection of the brain and death of the infected fly, while pharmacological activation of autophagy is protective. These data suggest an essential role for an inflammation-dependent STING pathway in the control of neuronal infection and a conserved role for STING in antimicrobial autophagy, which may represent an ancestral function for this essential innate immune sensor.
巻・号 24(1)
ページ 57-68.e3
公開日 2018-7-11
DOI 10.1016/j.chom.2018.05.022
PII S1931-3128(18)30276-2
PMID 29934091
PMC PMC6173519
MeSH Animals Anti-Infective Agents Autophagy / physiology* Brain / immunology* Brain / virology Cell Line Chlorocebus aethiops Disease Models, Animal Drosophila melanogaster / genetics Drosophila melanogaster / immunology* Drosophila melanogaster / virology Encephalitis / immunology Encephalitis / virology Female Humans Immunity, Innate* Inflammation / immunology* Male NF-kappa B / immunology Neurons / immunology Neurons / virology RNA Interference / immunology Signal Transduction / immunology* Vero Cells Zika Virus / pathogenicity Zika Virus Infection / immunology*
IF 15.923
引用数 56
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