Live and let die: ZBP1 senses viral and cellular RNAs to trigger necroptosis

Assil, Sonia; Paludan, Søren R

doi:10.15252/embj.201797845

Cited by 8 publications

(3 citation statements)

References 10 publications

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“…It is shown that M45 mutant viruses fail to infect mice [137,138] due to excessive activation of necroptosis [50,134]. In DAI/ZBP1-induced necroptosis, DAI/ZBP1senses viral RNA sensor [139] instead of DNA as previously thought [140]. It is shown that RIPK1 knockdown or inhibition fails to protect from MCMV-induced necroptosis, whereas inhibition of the viral transcriptional activator, immediate-early viral trans-activator (IE3) protected from MCMV-induced necroptosis [141].…”

Section: Dna Viruses Mediated Anti-necroptosismentioning

confidence: 99%

Revisiting Regulated Cell Death Responses in Viral Infections

Rex

Prasad

Kandasamy

2022

IJMS

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The fate of a viral infection in the host begins with various types of cellular responses, such as abortive, productive, latent, and destructive infections. Apoptosis, necroptosis, and pyroptosis are the three major types of regulated cell death mechanisms that play critical roles in viral infection response. Cell shrinkage, nuclear condensation, bleb formation, and retained membrane integrity are all signs of osmotic imbalance-driven cytoplasmic swelling and early membrane damage in necroptosis and pyroptosis. Caspase-driven apoptotic cell demise is considered in many circumstances as an anti-inflammatory, and some pathogens hijack the cell death signaling routes to initiate a targeted attack against the host. In this review, the selected mechanisms by which viruses interfere with cell death were discussed in-depth and were illustrated by compiling the general principles and cellular signaling mechanisms of virus–host-specific molecule interactions.

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Section: Dna Viruses Mediated Anti-necroptosismentioning

confidence: 99%

Revisiting Regulated Cell Death Responses in Viral Infections

Rex

Prasad

Kandasamy

2022

IJMS

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“…MCMV encodes M45 that disrupts the ZBP1‐RIPK3 interaction and blocks necroptosis activation upon MCMV infection (Figure 3B ). Using a mutated MCMV in M45 (MCMV‐M45 mutRHIM ), ZBP1‐mediated necroptosis is activated upon infection and, more importantly, this activation is induced by the newly transcribed RNA generated upon infection, which binds to the two Zα domains of ZBP1 [ 60 , 61 , 70 ]. Herpes simplex virus 1 (HSV1) triggers necroptosis via ZBP1, encoding ICP6 as the antagonism, with a mechanism reminiscent of MCMV [ 71 ] (Figure 3B ).…”

Section: Introductionmentioning

confidence: 99%

Z‐nucleic acids: Uncovering the functions from past to present

Tang

2022

Eur J Immunol

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Since Z-nucleic acid was identified in the 1970s, much is still unknown about its biological functions and nature in vivo. Recent studies on adenosine deaminase acting on RNA 1 (ADAR1) and Z-DNA-binding protein 1 (ZBP1) have highlighted its function in immune responses. Specifically, Z-RNAs, either endogenous or induced by viral infection, are sensed by ZBP1 and activate necroptosis. Z-RNAs act as the stimuli that induce innate immune responses through various pathways, including melanoma differentiationassociated protein 5 (MAD5)-mitochondrial antiviral-signaling protein (MAVS)-mediated type I IFN activation and proteinase kinase R (PKR)-dependent integrated stress response, and their immunostimulatory potential is curtailed by RNA editing conducted by ADAR1. Aberrant immune responses induced by Z-RNAs are associated with human diseases. They also induce pathogenesis in mice. Unlike Z-RNAs, the biological functions of Z-DNAs were barely studied, especially in mammals. Moreover, the origin or sequence preference of Z-nucleic acids requires further investigation. Such knowledge will expand our understanding of Z-nucleic acids, including from which genomic loci and under which circumstances they form, and the mechanisms by which they participate in the physiological activities. In this review, we provide insights in Z-nucleic acid research and highlight the unsolved puzzles.

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“…Much evidence shows that the Z-DNA of alternative pyrimidine purine (APP) sequences really exists in vivo and is associated with diverse diseases [3][4][5][6][7]. It has been shown that Z-DNA is involved in regulating gene expression, inducing chromosome recombination, and so on [8][9][10][11][12][13][14][15][16]. However, Z-DNA is hard to form without topological constraint or special conditions such as chemical modification or high salt concentrations because it is easily transferred to B-DNA.…”

Section: Introductionmentioning

confidence: 99%

Construction of ssDNA-Attached LR-Chimera Involving Z-DNA for ZBP1 Binding Analysis

Liang

2022

Molecules

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The binding of proteins to Z-DNA is hard to analyze, especially for short non-modified DNA, because it is easily transferred to B-DNA. Here, by the hybridization of a larger circular single-stranded DNA (ssDNA) with a smaller one, an LR-chimera (involving a left-handed part and a right-handed one) with an ssDNA loop is produced. The circular ssDNAs are prepared by the hybridization of two ssDNA fragments to form two nicks, followed by nick sealing with T4 DNA ligase. No splint (a scaffold DNA for circularizing ssDNA) is required, and no polymeric byproducts are produced. The ssDNA loop on the LR-chimera can be used to attach it with other molecules by hybridization with another ssDNA. The gel shift binding assay with Z-DNA specific binding antibody (Z22) or Z-DNA binding protein 1 (ZBP1) shows that stable Z-DNA can form under physiological ionic conditions even when the extra ssDNA part is present. Concretely, a 5′-terminal biotin-modified DNA oligonucleotide complementary to the ssDNA loop on the LR-chimera is used to attach it on the surface of a biosensor inlaid with streptavidin molecules, and the binding constant of ZBP1 with Z-DNA is analyzed by BLI (bio-layer interferometry). This approach is convenient for quantitatively analyzing the binding dynamics of Z-DNA with other molecules.

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Live and let die: ZBP1 senses viral and cellular RNAs to trigger necroptosis

Cited by 8 publications

References 10 publications

Revisiting Regulated Cell Death Responses in Viral Infections

Revisiting Regulated Cell Death Responses in Viral Infections

Z‐nucleic acids: Uncovering the functions from past to present

Construction of ssDNA-Attached LR-Chimera Involving Z-DNA for ZBP1 Binding Analysis

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