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

Li, Lili; Zhao, Hui; Liu, Ping; Li, Chunfeng; Quanquin, Natalie; Ji, Xue; Sun, Nina; Du, Pu; Qin, Cheng‐Feng; Lü, Ning; Cheng, Genhong

doi:10.1126/scisignal.aas9332

Cited by 92 publications

(96 citation statements)

References 59 publications

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“…First, many mammalian PARPs are stimulated by the production of IFN (IFN-stimulated genes [ISGs]), and thus are part of the mammalian antiviral defense system (Atasheva et al 2012;Zhang et al 2015;Eckei et al 2017;Li et al 2018;Grunewald et al 2019a). Also, several mono-ADP-ribosylating PARPs are rapidly evolving, indicating ongoing conflict with pathogens.…”

Section: Mammalian Parps Display Several Properties Indicative Of Invmentioning

confidence: 99%

The impact of PARPs and ADP-ribosylation on inflammation and host–pathogen interactions

et al. 2020

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Poly-adenosine diphosphate-ribose polymerases (PARPs) promote ADP-ribosylation, a highly conserved, fundamental posttranslational modification (PTM). PARP catalytic domains transfer the ADP-ribose moiety from NAD+ to amino acid residues of target proteins, leading to mono- or poly-ADP-ribosylation (MARylation or PARylation). This PTM regulates various key biological and pathological processes. In this review, we focus on the roles of the PARP family members in inflammation and host–pathogen interactions. Here we give an overview the current understanding of the mechanisms by which PARPs promote or suppress proinflammatory activation of macrophages, and various roles PARPs play in virus infections. We also demonstrate how innovative technologies, such as proteomics and systems biology, help to advance this research field and describe unanswered questions.

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Section: Mammalian Parps Display Several Properties Indicative Of Invmentioning

confidence: 99%

The impact of PARPs and ADP-ribosylation on inflammation and host–pathogen interactions

et al. 2020

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“…This group and others demonstrated that PARP12 could also inhibit vesicular stomatitis virus (VSV), Rift Valley fever virus (RVFV), and encephalomyocarditis virus (EMCV) [31,32]. PARP12 has been further shown to restrict Zika virus replication by promoting the degradation of viral proteins in an ADP-ribosylation-dependent manner [33]. PARP9 has been shown to complex with the DTX3L ubiquitin ligase to ubiquitinate the host histone H2BJ to enhance IFN signaling, resulting in the inhibition of RNA virus replication [34].…”

mentioning

confidence: 99%

The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression

et al. 2019

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ADP-ribosylation is a ubiquitous post-translational addition of either monomers or polymers of ADP-ribose to target proteins by ADP-ribosyltransferases, usually by interferon-inducible diphtheria toxin-like enzymes known as PARPs. While several PARPs have known antiviral activities, these activities are mostly independent of ADP-ribosylation. Consequently, less is known about the antiviral effects of ADP-ribosylation. Several viral families, including Coronaviridae, Togaviridae, and Hepeviridae, encode for macrodomain proteins that bind to and hydrolyze ADP-ribose from proteins and are critical for optimal replication and virulence. These results suggest that macrodomains counter cellular ADP-ribosylation, but whether PARPs or, alternatively, other ADP-ribosyltransferases cause this modification is not clear. Here we show that pan-PARP inhibition enhanced replication and inhibited interferon production in primary macrophages infected with macrodomain-mutant but not wild-type coronavirus. Specifically, knockdown of two abundantly expressed PARPs, PARP12 and PARP14, led to increased replication of mutant but did not significantly affect wild-type virus. PARP14 was also important for the induction of interferon in mouse and human cells, indicating a critical role for this PARP in the regulation of innate immunity. In summary, these data demonstrate that the macrodomain is required to prevent PARP-mediated inhibition of coronavirus replication and enhancement of interferon production.

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“…Our data showing that key components of this complex are part of the essential type I IFN system underscore its importance in the core antiviral response. Besides, other activities of PARP may be involved in antiviral mechanisms; for example PARP12 mediates ADP-ribosylation of Zika virus NS1 and NS3, leading to their degradation by the proteasome (57). The ADP-ribo-hydrolase encoded by the Chikungunya virus, that is required for its virulence, is another hint of the central importance of these enzymes in antiviral defense (58).…”

Section: Discussionmentioning

confidence: 99%

Interferon-stimulated genes in zebrafish and human define an ancient arsenal of antiviral immunity

Levraud

Jouneau

Briolat

et al. 2019

Preprint

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The evolution of the interferon (IFN) system, the major innate antiviral mechanism of vertebrates, remains poorly understood. According to the detection of type I IFN genes in cartilaginous fish genomes, the system appeared 500My ago. However, the IFN system integrates many other components, most of which are encoded by IFN-stimulated genes (ISGs). To shed light on its evolution, we have used deep RNA sequencing to generate a comprehensive list of ISGs of zebrafish, taking advantage of the high quality genome annotation in this species. We analyzed larvae after inoculation of recombinant zebrafish type I IFN, or infection with chikungunya virus, a potent IFN inducer. We identified more than 400 zebrafish ISGs, defined as being either directly induced by IFN or induced by the virus in an IFN receptor-dependent manner. Their human orthologues were highly enriched in ISGs, particularly for highly-inducible genes. We identified 72 orthology groups containing ISGs in both zebrafish and human, revealing a core ancestral ISG repertoire, which includes most of the known signaling components of the IFN system. Many downstream effectors were also already present 450 My ago in the common ancestor of tetrapods and bony fish, and diversified as multi-gene families independently in the two lineages. A large proportion of the ISG repertoire is lineage-specific; around 40% of protein-coding zebrafish ISGs had no human orthologue. We identified 14 fish-specific gene families containing multiple ISGs, including finTRIMs. This work illuminates the evolution of the IFN system and provides a rich resource to explore new antiviral mechanisms.Key pointsWe established an exhaustive list of larval zebrafish ISGs.Orthologous ISGs in fish and human identify a large ancestral ISG repertoire.

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

Cited by 92 publications

References 59 publications

The impact of PARPs and ADP-ribosylation on inflammation and host–pathogen interactions

The impact of PARPs and ADP-ribosylation on inflammation and host–pathogen interactions

The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression

Interferon-stimulated genes in zebrafish and human define an ancient arsenal of antiviral immunity

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