Identification of poly(ADP-ribose) polymerase 9 (PARP9) as a noncanonical sensor for RNA virus in dendritic cells

Xing, Junji; Zhang, Ao; Du, Yong; Fang, Mingli; Minze, Laurie J.; Liu, Yongjun; Li, Xian Chang; Zhang, Zhiqiang

doi:10.1038/s41467-021-23003-4

Cited by 71 publications

(85 citation statements)

References 67 publications

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“…Other reports also connect PARP9 to IFN signaling. PARP9 was recently discovered to be a non-canonical sensor for RNA viruses to promote type I IFN production via the phosphoinositide 3-kinase (PI3K)/AKT3 pathway ( Figure 4E ) [ 71 ]. Knockdown or deletion of PARP9 in dendritic cells, macrophages, or mice inhibits type I IFN production in response to double strand RNA (dsRNA) stimulation or RNA virus infection, including retrovirus, VSV, and IAV.…”

Section: The Roles Of Parps In Viral Infectionmentioning

confidence: 99%

“…Knockdown or deletion of PARP9 in dendritic cells, macrophages, or mice inhibits type I IFN production in response to double strand RNA (dsRNA) stimulation or RNA virus infection, including retrovirus, VSV, and IAV. Mechanistically, PARP9 uses its macrodomains for recognizing viral dsRNA, and interacts with PI3K p85 for activating downstream PI3K/AKT3 pathway, independent of mitochondrial antiviral-signaling (MAVS), limiting the RNA virus infection [ 71 ].…”

Section: The Roles Of Parps In Viral Infectionmentioning

confidence: 99%

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NAD+-consuming enzymes in immune defense against viral infection

Shang

Smith

Anmangandla

et al. 2021

Biochemical Journal

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The COVID-19 pandemic reminds us that in spite of the scientific progress in the past century, there is a lack of general antiviral strategies. In analogy to broad-spectrum antibiotics as antibacterial agents, developing broad spectrum antiviral agents would buy us time for the development of vaccines and treatments for future viral infections. In addition to targeting viral factors, a possible strategy is to understand host immune defense mechanisms and develop methods to boost the antiviral immune response. Here we summarize the role of NAD+-consuming enzymes in the immune defense against viral infections, with the hope that a better understanding of this process could help to develop better antiviral therapeutics targeting these enzymes. These NAD+-consuming enzymes include PARPs, sirtuins, CD38, and SARM1. Among these, the antiviral function of PARPs is particularly important and will be a focus of this review. Interestingly, NAD+ biosynthetic enzymes are also implicated in immune responses. In addition, many viruses, including SARS-CoV-2 contain a macrodomain-containing protein (NSP3 in SARS-CoV-2), which serves to counteract the antiviral function of host PARPs. Therefore, NAD+ and NAD+-consuming enzymes play crucial roles in immune responses against viral infections and detailed mechanistic understandings in the future will likely facilitate the development of general antiviral strategies.

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Section: The Roles Of Parps In Viral Infectionmentioning

confidence: 99%

Section: The Roles Of Parps In Viral Infectionmentioning

confidence: 99%

NAD+-consuming enzymes in immune defense against viral infection

Shang

Smith

Anmangandla

et al. 2021

Biochemical Journal

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“…PARPs are known ISGs and have shown to possess antiviral properties ( Zhu and Zheng, 2021 ). PAPR9 together with DTX3L promotes ISG expression during viral infection to enhance the immune response ( Zhang et al., 2015 ), and it has been suggested that PAPR9 serves as a non-canonical sensor for RNA virus to initiate and amplify type I IFN production in dendritic cells ( Xing et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Persistent coxsackievirus B1 infection triggers extensive changes in the transcriptome of human pancreatic ductal cells

Buchacher¹,

Honkimaa²,

Välikangas³

et al. 2022

iScience

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Summary Enteroviruses, particularly the group B coxsackieviruses (CVBs), have been associated with the development of type 1 diabetes. Several CVB serotypes establish chronic infections in human cells in vivo and in vitro . However, the mechanisms leading to enterovirus persistency and, possibly, beta cell autoimmunity are not fully understood. We established a carrier-state-type persistent infection model in human pancreatic cell line PANC-1 using two distinct CVB1 strains and profiled the infection-induced changes in cellular transcriptome. In the current study, we observed clear changes in the gene expression of factors associated with the pancreatic microenvironment, the secretory pathway, and lysosomal biogenesis during persistent CVB1 infections. Moreover, we found that the antiviral response pathways were activated differently by the two CVB1 strains. Overall, our study reveals extensive transcriptional responses in persistently CVB1-infected pancreatic cells with strong opposite but also common changes between the two strains.

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“…In addition to the mitochondria, MAVS has also been found on peroxisomes, where it can induce a unique signaling pathway that specifically triggers IFNλ expression but not IFNβ in response to certain viral infections (Dixit et al, 2010;Odendall et al, 2014;Bender et al, 2015). Another sensor of RNA virus infection in Mϕ is poly ADPribose polymerase 9 (PARP9) (Xing et al, 2021). Interestingly, PARP9 is required to control RNA virus infection in STAT1dependent signal transduction, enhancing IFN-regulated host responses (Zhang et al, 2015).…”

Section: Viral Tricks To Avoid Pathogen Recognition Receptors Activationmentioning

confidence: 99%

“…Another sensor of RNA virus infection in Mφ is poly ADP-ribose polymerase 9 (PARP9) ( Xing et al, 2021 ). Interestingly, PARP9 is required to control RNA virus infection in STAT1-dependent signal transduction, enhancing IFN-regulated host responses ( Zhang et al, 2015 ).…”

Section: Viral Tricks To Avoid Pathogen Recognition Receptors Activationmentioning

confidence: 99%

The Activated Macrophage – A Tough Fortress for Virus Invasion: How Viruses Strike Back

et al. 2022

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Macrophages (Mφ) are innate immune cells with a variety of functional phenotypes depending on the cytokine microenvironment they reside in. Mφ exhibit distinct activation patterns that are found within a wide array of activation states ranging from the originally discovered classical pro-inflammatory (M1) to the anti-inflammatory (M2) with their multi-facades. M1 cells are induced by IFNγ + LPS, while M2 are further subdivided into M2a (IL-4), M2b (Immune Complex) and M2c (IL-10) based on their inducing stimuli. Not surprisingly, Mφ activation influences the outcome of viral infections as they produce cytokines that in turn activate cells of the adaptive immune system. Generally, activated M1 cells tend to restrict viral replication, however, influenza and HIV exploit inflammation to support their replication. Moreover, M2a polarization inhibits HIV replication at the post-integration level, while HCMV encoded hrIL-10 suppresses inflammatory reactions by facilitating M2c formation. Additionally, viruses such as LCMV and Lassa Virus directly suppress Mφ activation leading to viral chronicity. Here we review how Mφ activation affects viral infection and the strategies by which viruses manipulate Mφ polarization to benefit their own fitness. An understanding of these mechanisms is important for the development of novel immunotherapies that can sway Mφ phenotype to inhibit viral replication.

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Identification of poly(ADP-ribose) polymerase 9 (PARP9) as a noncanonical sensor for RNA virus in dendritic cells

Cited by 71 publications

References 67 publications

NAD+-consuming enzymes in immune defense against viral infection

NAD+-consuming enzymes in immune defense against viral infection

Persistent coxsackievirus B1 infection triggers extensive changes in the transcriptome of human pancreatic ductal cells

The Activated Macrophage – A Tough Fortress for Virus Invasion: How Viruses Strike Back

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