Antiviral activity of bacterial TIR domains via signaling molecules that trigger cell death

2021 ◽  
Author(s):  
Jonny Coates
Keyword(s):  
Cell Death ◽  
Antiviral Activity ◽  
Signaling Molecules ◽  
Tir Domains ◽  
Trigger Cell Death

scholarly journals Antiviral activity of bacterial TIR domains via signaling molecules that trigger cell death

2021 ◽  
Author(s):  
Gal Ofir ◽  
Ehud Herbst ◽  
Maya Baroz ◽  
Daniel Cohen ◽  
Adi Millman ◽  
...  
Keyword(s):  
Cell Death ◽  
Intracellular Signaling ◽  
Interleukin 1 ◽  
Signaling Molecules ◽  
Immune Systems ◽  
Tir Domain ◽  
Cyclic Adp Ribose ◽  
Molecular Signal ◽  
Tir Domains ◽  
Intracellular Signaling Molecules

AbstractThe Toll/interleukin-1 receptor (TIR) domain is a canonical component of animal and plant immune systems. In plants, intracellular pathogen sensing by immune receptors triggers their TIR domains to generate a molecule which is a variant of cyclic ADP-ribose (v-cADPR). This molecule is hypothesized to activate plant cell death via a yet unresolved pathway. TIR domains were recently also shown to be involved in a bacterial anti-phage defense system called Thoeris, but the mechanism of Thoeris defense remained unknown. In this study we report that phage infection triggers Thoeris TIR-domain proteins to produce an isomer of cyclic ADP-ribose. This molecular signal activates a second protein, ThsA, which then depletes the cell of the essential molecule nicotinamide adenine dinucleotide (NAD) and leads to abortive infection and cell death. We further show that similar to eukaryotic innate immune systems, bacterial TIR-domain proteins determine the immunological specificity to the invading pathogen. Our results describe a new antiviral signaling pathway in bacteria, and suggest that generation of intracellular signaling molecules is an ancient immunological function of TIR domains conserved in both plant and bacterial immunity.

Inhibition of Autophagy Potentiated Hippocampal Cell Death Induced by Endoplasmic Reticulum Stress and its Activation by Trehalose Failed to be Neuroprotective

2019 ◽  
Vol 16 (1) ◽  
pp. 3-11
Author(s):  
Luisa Halbe ◽  
Abdelhaq Rami
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Cell Damage ◽  
Protective Mechanism ◽  
Unfolded Proteins ◽  
Neuronal Viability ◽  
Hippocampal Cell ◽  
Trigger Cell Death ◽  
Autophagy Inhibition

Introduction: Endoplasmic reticulum (ER) stress induced the mobilization of two protein breakdown routes, the proteasomal- and autophagy-associated degradation. During ERassociated degradation, unfolded ER proteins are translocated to the cytosol where they are cleaved by the proteasome. When the accumulation of misfolded or unfolded proteins excels the ER capacity, autophagy can be activated in order to undertake the degradative machinery and to attenuate the ER stress. Autophagy is a mechanism by which macromolecules and defective organelles are included in autophagosomes and delivered to lysosomes for degradation and recycling of bioenergetics substrate. Materials and Methods: Autophagy upon ER stress serves initially as a protective mechanism, however when the stress is more pronounced the autophagic response will trigger cell death. Because autophagy could function as a double edged sword in cell viability, we examined the effects autophagy modulation on ER stress-induced cell death in HT22 murine hippocampal neuronal cells. We investigated the effects of both autophagy-inhibition by 3-methyladenine (3-MA) and autophagy-activation by trehalose on ER-stress induced damage in hippocampal HT22 neurons. We evaluated the expression of ER stress- and autophagy-sensors as well as the neuronal viability. Results and Conclusion: Based on our findings, we conclude that under ER-stress conditions, inhibition of autophagy exacerbates cell damage and induction of autophagy by trehalose failed to be neuroprotective.

scholarly journals Short-term intense Bcr–Abl kinase inhibition with nilotinib is adequate to trigger cell death in BCR-ABL+ cells

Leukemia ◽  
2009 ◽  
Vol 23 (6) ◽  
pp. 1205-1206 ◽  
Author(s):  
D K Hiwase ◽  
D L White ◽  
V A Saunders ◽  
S Kumar ◽  
J V Melo ◽  
...  
Keyword(s):  
Cell Death ◽  
Short Term ◽  
Kinase Inhibition ◽  
Abl Kinase ◽  
Trigger Cell Death

Stilbene–Chalcone Hybrids: Design, Synthesis, and Evaluation as a New Class of Antimalarial Scaffolds That Trigger Cell Death through Stage Specific Apoptosis

2011 ◽  
Vol 55 (1) ◽  
pp. 297-311 ◽  
Author(s):  
Naina Sharma ◽  
Dinesh Mohanakrishnan ◽  
Amit Shard ◽  
Abhishek Sharma ◽  
Saima ◽  
...  
Keyword(s):  
Cell Death ◽  
Design Synthesis ◽  
New Class ◽  
Trigger Cell Death

PPE11 of Mycobacterium tuberculosis can alter host inflammatory response and trigger cell death

2019 ◽  
Vol 126 ◽  
pp. 45-55 ◽  
Author(s):  
Xuan Peng ◽  
Tao Luo ◽  
Xiaoqian Zhai ◽  
Chunxi Zhang ◽  
Jing Suo ◽  
...  
Keyword(s):  
Cell Death ◽  
Mycobacterium Tuberculosis ◽  
Inflammatory Response ◽  
Trigger Cell Death ◽  
Host Inflammatory Response

scholarly journals Activation and Antagonism of the OAS–RNase L Pathway

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 14
Author(s):  
Susan R. Weiss
Keyword(s):  
Cell Death ◽  
Antiviral Activity ◽  
Apoptotic Cell ◽  
Early Response ◽  
Apoptotic Cell Death ◽  
Rnase L ◽  
Oligoadenylate Synthetase ◽  
Viral Genomes ◽  
L System ◽  
Infected Cells

The oligoadenylate synthetase–ribonuclease L (OAS–RNase L) system is a potent antiviral pathway that severely limits the pathogenesis of many viruses. Upon sensing dsRNA, OASs produce 2′,5′-oligoadenylates (2-5A) that activate RNase L to cleave both host and viral single-stranded RNA, thereby limiting protein production, virus replication and spread, leading to apoptotic cell death. Endogenous host dsRNA, which accumulates in the absence of adenosine deaminase acting on RNA (ADAR)1, can also activate RNase L and lead to apoptotic cell death. RNase L activation and antiviral activity during infections with several types of viruses in human and bat cells is dependent on OAS3 but independent of virus-induced interferon (IFN) and, thus, RNase L can be activated even in the presence of IFN antagonists. Differently from other human viruses examined, Zika virus is resistant to the antiviral activity of RNase L and instead utilizes RNase L to enhance its replication factories to produce more infectious virus. Some betacoronaviruses antagonize RNase L activation by expressing 2′,5′-phosphodiesterases (PDEs) that cleave 2-5A and thereby antagonize activation of RNase L. The best characterized of these PDEs is the murine coronavirus (MHV) NS2 accessory protein. Enzymatically active NS2 is required for replication in myeloid cells and in the liver. Interestingly, while wild type mice clear MHV from the liver by 7–10 days post-infection, RNase L knockout mice fail to effectively clear MHV, probably due to diminished apoptotic death of infected cells. We suggest that RNase L antiviral activity stems from direct cleavage of viral genomes and cessation of protein synthesis as well as through promoting death of infected cells, limiting the spread of virus. Importantly, OASs are pattern recognition receptors and the OAS–RNase L pathway is a primary innate response pathway to viruses, capable of early response, coming into play before IFN is induced or when the virus shuts down IFN signaling.

scholarly journals ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death

2017 ◽  
Vol 214 (8) ◽  
pp. 2217-2229 ◽  
Author(s):  
Sannula Kesavardhana ◽  
Teneema Kuriakose ◽  
Clifford S. Guy ◽  
Parimal Samir ◽  
R.K. Subbarao Malireddi ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Posttranslational Modifications ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Dna Binding Protein ◽  
Cell Death Pathways ◽  
Signaling Axis ◽  
Trigger Cell Death ◽  
Inducible Gene

Innate sensing of influenza virus infection induces activation of programmed cell death pathways. We have recently identified Z-DNA–binding protein 1 (ZBP1) as an innate sensor of influenza A virus (IAV). ZBP1-mediated IAV sensing is critical for triggering programmed cell death in the infected lungs. Surprisingly, little is known about the mechanisms regulating ZBP1 activation to induce programmed cell death. Here, we report that the sensing of IAV RNA by retinoic acid inducible gene I (RIG-I) initiates ZBP1-mediated cell death via the RIG-I–MAVS–IFN-β signaling axis. IAV infection induces ubiquitination of ZBP1, suggesting potential regulation of ZBP1 function through posttranslational modifications. We further demonstrate that ZBP1 senses viral ribonucleoprotein (vRNP) complexes of IAV to trigger cell death. These findings collectively indicate that ZBP1 activation requires RIG-I signaling, ubiquitination, and vRNP sensing to trigger activation of programmed cell death pathways during IAV infection. The mechanism of ZBP1 activation described here may have broader implications in the context of virus-induced cell death.

Slow Regulated Release of H2S Inhibits Oxidative Stress Induced Cell Death by Influencing Certain Key Signaling Molecules

2013 ◽  
Vol 38 (7) ◽  
pp. 1375-1393 ◽  
Author(s):  
Aman Shah Abdul Majid ◽  
Amin Malik Shah Abdul Majid ◽  
Zheng Qin Yin ◽  
Dan Ji
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Signaling Molecules
Sign in / Sign up

Export Citation Format

Share Document