Type I interferons and endoplasmic reticulum stress in health and disease

Sprooten, Jenny; Garg, Abhishek D.

doi:10.1016/bs.ircmb.2019.10.004

Cited by 64 publications

(47 citation statements)

References 492 publications

(598 reference statements)

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“…It is hypothesized that DMV structures more efficiently concentrate newly synthesized viral RNA genomes with associated virion structural proteins to better enable virus assembly and packaging. DMV could also serve to shield viral genome RNAs from recognition and destruction by innate cellular defense systems [ 40 , 41 ]. In concert with host cell ER factors and an increase in fatty acid synthesis [ 37 ], the SARS-CoV-2 nonstructural proteins (nsp)3, 4, 6 construct the replication organelle structures [ 42 , 43 ].…”

Section: The Essential Role Of Lipids During Sars-cov-2 Replicatiomentioning

confidence: 99%

The Fatty Acid Lipid Metabolism Nexus in COVID-19

Tanner

Alfieri

2021

Viruses

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Enteric symptomology seen in early-stage severe acute respiratory syndrome (SARS)-2003 and COVID-19 is evidence of virus replication occurring in the intestine, liver and pancreas. Aberrant lipid metabolism in morbidly obese individuals adversely affects the COVID-19 immune response and increases disease severity. Such observations are in line with the importance of lipid metabolism in COVID-19, and point to the gut as a site for intervention as well as a therapeutic target in treating the disease. Formation of complex lipid membranes and palmitoylation of coronavirus proteins are essential during viral replication and assembly. Inhibition of fatty acid synthase (FASN) and restoration of lipid catabolism by activation of AMP-activated protein kinase (AMPK) impede replication of coronaviruses closely related to SARS-coronavirus-2 (CoV-2). In vitro findings and clinical data reveal that the FASN inhibitor, orlistat, and the AMPK activator, metformin, may inhibit coronavirus replication and reduce systemic inflammation to restore immune homeostasis. Such observations, along with the known mechanisms of action for these types of drugs, suggest that targeting fatty acid lipid metabolism could directly inhibit virus replication while positively impacting the patient’s response to COVID-19.

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Section: The Essential Role Of Lipids During Sars-cov-2 Replicatiomentioning

confidence: 99%

The Fatty Acid Lipid Metabolism Nexus in COVID-19

Tanner

Alfieri

2021

Viruses

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“…In fact, a recent study proposed that cytokine production may even continue in the necroptotic cells after the loss of plasma membrane integrity at the level of the endoplasmic reticulum (ER), which remains intact for a relatively longer time after cellular disruption [131]. Although it is not clear whether all these cytokines are sufficiently mature or functional, since they skip post-ER maturation steps and thus exist in "native or immature" form [132]. Nevertheless, these insights underscore the heightened inflammatory potential of necroptosis.…”

Section: Necroptosis and Inflammationmentioning

confidence: 99%

Necroptosis in Immuno-Oncology and Cancer Immunotherapy

Sprooten

Wijngaert

Vanmeerbeek

et al. 2020

Cells

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Immune-checkpoint blockers (ICBs) have revolutionized oncology and firmly established the subfield of immuno-oncology. Despite this renaissance, a subset of cancer patients remain unresponsive to ICBs due to widespread immuno-resistance. To “break” cancer cell-driven immuno-resistance, researchers have long floated the idea of therapeutically facilitating the immunogenicity of cancer cells by disrupting tumor-associated immuno-tolerance via conventional anticancer therapies. It is well appreciated that anticancer therapies causing immunogenic or inflammatory cell death are best positioned to productively activate anticancer immunity. A large proportion of studies have emphasized the importance of immunogenic apoptosis (i.e., immunogenic cell death or ICD); yet, it has also emerged that necroptosis, a programmed necrotic cell death pathway, can also be immunogenic. Emergence of a proficient immune profile for necroptosis has important implications for cancer because resistance to apoptosis is one of the major hallmarks of tumors. Putative immunogenic or inflammatory characteristics driven by necroptosis can be of great impact in immuno-oncology. However, as is typical for a highly complex and multi-factorial disease like cancer, a clear cause versus consensus relationship on the immunobiology of necroptosis in cancer cells has been tough to establish. In this review, we discuss the various aspects of necroptosis immunobiology with specific focus on immuno-oncology and cancer immunotherapy.

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“…Another level of immune-dysregulation during COVID-19 is positioned at the antiviral immunity induced by SARS-CoV-2-infected cells. A normal antiviral response involves a sustained type I/III interferon (IFN) cytokine-response that activates IFN-stimulated-genes (ISGs), which then orchestrate a multi-parametric program of antiviral defenses ( 2 , 15 ). SARS-CoV-2 can disrupt these protective inflammatory reactions by blunting type I/III IFN-cytokines, while increasing other pro-inflammatory cytokines ( 6 , 7 ).…”

Section: Sars-cov-2: From Cellular Pathogenesis To Immunological Consmentioning

confidence: 99%