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
|
リソース情報 |
ショウジョウバエ |
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