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| Status |
Public on Apr 28, 2024 |
| Title |
Zika Virus Non-Coding RNAs Antagonize Antiviral Responses by PKR-Mediated Translational Arrest (Ribo-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that causes severe outbreaks in human populations. ZIKV infection leads to the accumulation of small non-coding viral RNAs (known as sfRNAs) that are crucial for evasion of antiviral responses and for viral pathogenesis. However, the mechanistic understanding of how sfRNAs function remains incomplete. Here, we use recombinant ZIKVs and ribosome profiling of infected human cells to show that sfRNAs block translation of antiviral genes. Mechanistically, we demonstrate that specific RNA structures present in sfRNAs trigger PKR activation, which instead of limiting viral replication, enhances viral particle production. Although ZIKV infection induces mRNA expression of antiviral genes, translation efficiency of type I interferon and interferon stimulated genes were significantly downregulated by PKR activation. Our results reveal a novel viral adaptation mechanism mediated by sfRNAs, where ZIKV increases its fitness by repurposing the antiviral role of PKR into a proviral factor.
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| Overall design |
To investigate the effect of sfRNAs accumulation on the translation landscape of the cell host, we created a recombinant ZIKV incapable of producing sfRNAs (ZIKV sfRNAnull) by introducing mutations into the full-length cDNA of ZIKV ARCB116141 (pZIKVAr). Subsequently, we infected the A549 human cell line with both ZIKV WT and ZIKV sfRNAnull at an MOI=10. Ribosome Profiling and RNA-seq analyses were then performed on mock-infected and ZIKV-infected cells at 20 hours post-infection, utilizing data obtained from 2 replicates for each condition.
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| Contributor(s) |
Pallarés HM, González López Ledesma MM, Oviedo Rouco S, Castellano LA, Costa Navarro GS, Fernández-Alvarez AJ, D’Andreiz MJ, Aldas-Bulos VD, Alvarez DE, Bazzini A, Gamarnik AV |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Jan 25, 2024 |
| Last update date |
Apr 29, 2024 |
| Contact name |
Horacio Martín Pallarés |
| E-mail(s) |
homar.palla@gmail.com
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| Phone |
+5491158789299
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| Organization name |
Fundación instituto leloir
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| Lab |
Laboratorio de virología
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| Street address |
Av patricias argentinas 435
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| City |
Ciudad de Buenos Aires |
| ZIP/Postal code |
1405 |
| Country |
Argentina |
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| Platforms (1) |
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| Samples (6)
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| GSM8036805 |
A549 cells mock infected replicate 1 Ribo-seq |
| GSM8036806 |
A549 cells mock infected replicate 2 Ribo-seq |
| GSM8036807 |
A549 cells infected with ZIKV WT replicate 1 Ribo-seq |
| GSM8036808 |
A549 cells infected with ZIKV WT replicate 2 Ribo-seq |
| GSM8036809 |
A549 cells infected with ZIKV sfRNAnull replicate 1 Ribo-seq |
| GSM8036810 |
A549 cells infected with ZIKV sfRNAnull replicate 2 Ribo-seq |
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| This SubSeries is part of SuperSeries: |
| GSE254254 |
Zika Virus Non-Coding RNAs Antagonize Antiviral Responses by PKR-Mediated Translational Arrest |
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| Relations |
| BioProject |
PRJNA1069085 |
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