RIG-I Plays a Dominant Role in the Induction of Transcriptional Changes in Zika Virus-Infected Cells, which Protect from Virus-Induced Cell Death.
Animals
Cell Death
/ physiology
Chlorocebus aethiops
/ virology
DEAD Box Protein 58
/ metabolism
Humans
Immunity, Innate
/ immunology
Receptors, Immunologic
/ metabolism
Signal Transduction
/ immunology
Vero Cells
/ virology
Viral Nonstructural Proteins
/ metabolism
Zika Virus
/ immunology
Zika Virus Infection
/ immunology
IFN
IFNAR1
MDA5
NS5
RIG-I
Zika virus
apoptosis
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
16 06 2020
16 06 2020
Historique:
received:
15
05
2020
revised:
08
06
2020
accepted:
13
06
2020
entrez:
21
6
2020
pubmed:
21
6
2020
medline:
10
4
2021
Statut:
epublish
Résumé
The Zika virus (ZIKV) has received much attention due to an alarming increase in cases of neurological disorders including congenital Zika syndrome associated with infection. To date, there is no effective treatment available. An immediate response by the innate immune system is crucial for effective control of the virus. Using CRISPR/Cas9-mediated knockouts in A549 cells, we investigated the individual contributions of the RIG-I-like receptors MDA5 and RIG-I to ZIKV sensing and control of this virus by using a Brazilian ZIKV strain. We show that RIG-I is the main sensor for ZIKV in A549 cells. Surprisingly, we observed that loss of RIG-I and consecutive type I interferon (IFN) production led to virus-induced apoptosis. ZIKV non-structural protein NS5 was reported to interfere with type I IFN receptor signaling. Additionally, we show that ZIKV NS5 inhibits type I IFN induction. Overall, our study highlights the importance of RIG-I-dependent ZIKV sensing for the prevention of virus-induced cell death and shows that NS5 inhibits the production of type I IFN.
Identifiants
pubmed: 32560274
pii: cells9061476
doi: 10.3390/cells9061476
pmc: PMC7349056
pii:
doi:
Substances chimiques
Receptors, Immunologic
0
Viral Nonstructural Proteins
0
RIGI protein, human
EC 3.6.1.-
DEAD Box Protein 58
EC 3.6.4.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MC_UU_00008/8
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 100954
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12014/8
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N017552/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
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