The involvement of regulated cell death forms in modulating the bacterial and viral pathogenesis

Imre, Gergely

doi:10.1016/bs.ircmb.2019.12.008

Cited by 16 publications

(10 citation statements)

References 198 publications

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“…Recent findings have highlighted necroptosis as the predominant form of ICD in viral infections, such as in the case of the respiratory influenza A and neuropathogenic coronaviruses [52]. Moreover, a current study by Simpson et al proves for the first time that respiratory syncytial virus infection induces the release of the inflammatory nuclear alarmin HMGB1 (high mobility group box 1).…”

Section: Discussionmentioning

confidence: 64%

Primidone blocks RIPK1-driven cell death and inflammation

et al. 2020

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The receptor-interacting serine/threonine protein kinase 1 (RIPK1) is a key mediator of regulated cell death and inflammation. Recent studies suggest that RIPK1 inhibition would fundamentally improve the therapy of RIPK1-dependent organ damage in stroke, myocardial infarction, kidney failure, and systemic inflammatory response syndrome. Additionally, it could ameliorate or prevent multi-organ failure induced by cytokine release in the context of hyperinflammation, as seen in COVID-19 patients. Therefore, we searched for a RIPK1 inhibitor and present the aromatic antiepileptic and FDA-approved drug primidone (Liskantin®) as a potent inhibitor of RIPK1 activation in vitro and in a murine model of TNFα-induced shock, which mimics the hyperinflammatory state of cytokine release syndrome. Furthermore, we detected for the first time RIPK1 activation in the respiratory tract epithelium of hospitalized patients who tested positive for SARS-CoV-2 infection. Our data provide a strong rationale for evaluating the drug primidone in conditions of hyperinflammation in humans.

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Section: Discussionmentioning

confidence: 64%

Primidone blocks RIPK1-driven cell death and inflammation

et al. 2020

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“…Intracellular bacteria and also viruses can inhibit TNF-R1 internalization to prevent apoptotic killing of the host cells and thereby evade elimination by the host immune system. It is not known if these processes also involve palmitoylation or alterations in membrane lipid composition [ 42 , 43 , 44 , 45 , 46 ]. The P. aeruginosa quorum-sensing molecule 3oc, however, interacts with the PM of human cells.…”

Section: Roles Of Palmitoylation and Lipid Rafts In Tnf-r1 Signalingmentioning

confidence: 99%

Regulation of Death Receptor Signaling by S-Palmitoylation and Detergent-Resistant Membrane Micro Domains—Greasing the Gears of Extrinsic Cell Death Induction, Survival, and Inflammation

Fritsch

Särchen

Schneider-Brachert

2021

Cancers

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Death-receptor-mediated signaling results in either cell death or survival. Such opposite signaling cascades emanate from receptor-associated signaling complexes, which are often formed in different subcellular locations. The proteins involved are frequently post-translationally modified (PTM) by ubiquitination, phosphorylation, or glycosylation to allow proper spatio-temporal regulation/recruitment of these signaling complexes in a defined cellular compartment. During the last couple of years, increasing attention has been paid to the reversible cysteine-centered PTM S-palmitoylation. This PTM regulates the hydrophobicity of soluble and membrane proteins and modulates protein:protein interaction and their interaction with distinct membrane micro-domains (i.e., lipid rafts). We conclude with which functional and mechanistic roles for S-palmitoylation as well as different forms of membrane micro-domains in death-receptor-mediated signal transduction were unraveled in the last two decades.

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“…In contrast, necrosis is characterized by early membrane rupture of the cells. In the past decades, it became evident that necrotic-like cell death modalities can be also considered as a regulated process ( Vanden Berghe et al., 2014 ) and that they play a crucial role in response to various virus infections ( Imre, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

The sphingosine kinase 1 activator, K6PC-5, attenuates Ebola virus infection

et al. 2021

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Summary Ebola virus (EBOV) is responsible for outbreaks with case fatality rates of up to 90% and for an epidemic in West Africa with more than ten thousand deaths. EBOV glycoprotein (EBOV-GP) is the only viral surface protein and is responsible for viral entry into cells. Here, by employing pseudotyped EBOV-GP viral particles, we uncover a critical role for sphingolipids in inhibiting viral entry. Sphingosine kinase 1 (SphK1) catalyzes the phosphorylation of sphingosine to sphingosine 1-phosphate (S1P). The administration of the SphK1 activator, K6PC-5, or S1P, or the overexpression of SphK1 consistently exhibited striking inhibitory effects in EBOV-GP-driven entry in diverse cell lines. Finally, K6PC-5 markedly reduced the EBOV titer in infected cells and the de novo production of viral proteins. These data present K6PC-5 as an efficient tool to inhibit EBOV infection in endothelial cells and suggest further studies to evaluate its systemic effects.

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The involvement of regulated cell death forms in modulating the bacterial and viral pathogenesis

Cited by 16 publications

References 198 publications

Primidone blocks RIPK1-driven cell death and inflammation

Primidone blocks RIPK1-driven cell death and inflammation

Regulation of Death Receptor Signaling by S-Palmitoylation and Detergent-Resistant Membrane Micro Domains—Greasing the Gears of Extrinsic Cell Death Induction, Survival, and Inflammation

The sphingosine kinase 1 activator, K6PC-5, attenuates Ebola virus infection

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