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Series GSE162688 Query DataSets for GSE162688
Status Public on Sep 08, 2021
Title Antagonism of mitophagy by Zika virus reveals Ajuba as a regulator of PINK1-Parkin signaling and PKR-dependent inflammation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Dysregulated inflammation is a key driver of disease following infection with the globally important human pathogens, Zika virus (ZIKV) and dengue virus. However, specific mechanisms of inflammation are not well defined. Here, we demonstrate that ZIKV antagonizes mitophagy, or the process of selective degradation of damaged mitochondria. The mechanism of antagonism was through interactions between NS5 and the host protein Ajuba to prevent Ajuba translocation to depolarized mitochondria. We further identify a role of Ajuba in mitophagy through augmenting PINK1 kinase activity. Mitophagy suppression in infected Ajuba-/- cells amplified the cellular integrated stress response (ISR) to promote ZIKV replication, and increased pro-inflammatory cytokine expression dependent on the ISR kinase, PKR. Thus, ZIKV suppresses mitophagy to favor replication and this failure of mitochondrial quality control is translated to inflammation by PKR, suggesting new therapeutic targets to treat flavivirus disease.
 
Overall design 18,samples,total,,mouse,embryonic,fibroblasts,generated,from,3,different,mice,(WT,,PINK-/-,,Ajuba-/-),either,ZIKV,infected,or,mock,infected,,each,done,in,triplicate
 
Contributor(s) Ponia SS, Robertson SJ, McNally KL, Sturdevant GL, Lewis M, Jessop F, Bosio CM, Kendall C, Gallegos D, Hay A, Schwartz C, Rosenke R, Saturday G, Martens C, Best SM
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Submission date Dec 04, 2020
Last update date Sep 08, 2021
Contact name Craig Martens
E-mail(s) martensc@niaid.nih.gov
Phone 406-363-9415
Organization name NIAID
Department DIR
Lab RTB
Street address 903 S. 4th St
City Hamilton
State/province MT
ZIP/Postal code 59840
Country USA
 
Platforms (1)
GPL21626 NextSeq 550 (Mus musculus)
Samples (18)
GSM4957164 Ajuba_KO_Mock_R1
GSM4957165 Ajuba_KO_Mock_R3
GSM4957166 PINK1_KO_Mock_R3
Relations
BioProject PRJNA682614
SRA SRP295933

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE162688_normalized_counts.txt.gz 1.6 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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