PARP12 suppresses Zika virus infection through PARP-dependent degradation of NS1 and NS3 viral proteins

Zika virus infection stimulates a type I interferon (IFN) response in host cells, which suppresses viral replication. Type I IFNs exert antiviral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). To screen for antiviral ISGs that restricted Zika virus replication, we ind...

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Bibliographic Details
Published in:Science signaling 2018-06, Vol.11 (535)
Main Authors: Li, Lili, Zhao, Hui, Liu, Ping, Li, Chunfeng, Quanquin, Natalie, Ji, Xue, Sun, Nina, Du, Peishuang, Qin, Cheng-Feng, Lu, Ning, Cheng, Genhong
Format: Article
Language:English
Subjects:
A549 Cells
Adenosine diphosphate
ADP-Ribosylation
Animals
Antiviral activity
CRISPR
Degradation
Dogs
Drug development
Gene expression
Genes
Humans
Infections
Interferon
Interferon Regulatory Factors - genetics
Interferon Regulatory Factors - metabolism
Interferon Type I - genetics
Interferon Type I - metabolism
Lung cancer
Madin Darby Canine Kidney Cells
Mice
Molecular chains
Pharmacology
Poly(ADP-ribose) polymerase
Poly(ADP-ribose) Polymerases - metabolism
Proteasome Endopeptidase Complex - metabolism
Proteasomes
Proteins
Proteolysis
Replication
Ribosylation
RNA Helicases - metabolism
Serine Endopeptidases - metabolism
Ubiquitin
Ubiquitin - metabolism
Vector-borne diseases
Viral infections
Viral Nonstructural Proteins - metabolism
Virus Replication
Viruses
Zika virus
Zika Virus - physiology
Zika Virus Infection - metabolism
Zika Virus Infection - prevention & control
Zika Virus Infection - virology
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Summary:Zika virus infection stimulates a type I interferon (IFN) response in host cells, which suppresses viral replication. Type I IFNs exert antiviral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). To screen for antiviral ISGs that restricted Zika virus replication, we individually knocked out 21 ISGs in A549 lung cancer cells and identified PARP12 as a strong inhibitor of Zika virus replication. Our findings suggest that PARP12 mediated the ADP-ribosylation of NS1 and NS3, nonstructural viral proteins that are involved in viral replication and modulating host defense responses. This modification of NS1 and NS3 triggered their proteasome-mediated degradation. These data increase our understanding of the antiviral activity of PARP12 and suggest a molecular basis for the potential development of therapeutics against Zika virus.
ISSN:1945-0877
1937-9145
DOI:10.1126/scisignal.aas9332