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Your search keyword '"Ottosen, Rasmus"' showing total 3 results
Start Over Author "Ottosen, Rasmus" Publisher nature pub. group
3 results on '"Ottosen, Rasmus"'

1. Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways.

Author

Kurmasheva N, Said A, Wong B, Kinderman P, Han X, Rahimic AHF, Kress A, Carter-Timofte ME, Holm E, van der Horst D, Kollmann CF, Liu Z, Wang C, Hoang HD, Kovalenko E, Chrysopoulou M, Twayana KS, Ottosen RN, Svenningsen EB, Begnini F, Kiib AE, Kromm FEH, Weiss HJ, Di Carlo D, Muscolini M, Higgins M, van der Heijden M, Bardoul A, Tong T, Ozsvar A, Hou WH, Schack VR, Holm CK, Zheng Y, Ruzek M, Kalucka J, de la Vega L, Elgaher WAM, Korshoej AR, Lin R, Hiscott J, Poulsen TB, O'Neill LA, Roy DG, Rinschen MM, van Montfoort N, Diallo JS, Farin HF, Alain T, and Olagnier D

Subjects
Animals, Humans, Mice, Cell Line, Tumor, Interferon Type I metabolism, NF-E2-Related Factor 2 metabolism, Colonic Neoplasms therapy, Colonic Neoplasms immunology, Colonic Neoplasms drug therapy, Antiviral Agents pharmacology, NF-kappa B metabolism, I-kappa B Kinase metabolism, Kelch-Like ECH-Associated Protein 1 metabolism, Inflammation drug therapy, Female, Vesicular stomatitis Indiana virus physiology, Vesicular stomatitis Indiana virus drug effects, Signal Transduction drug effects, Oncolytic Virotherapy methods, Succinates pharmacology, Oncolytic Viruses
Abstract

The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKβ independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses., (© 2024. The Author(s).)

Published
2024
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2. Author Correction: SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate.

Author

Olagnier D, Farahani E, Thyrsted J, Blay-Cadanet J, Herengt A, Idorn M, Hait A, Hernaez B, Knudsen A, Iversen MB, Schilling M, Jørgensen SE, Thomsen M, Reinert LS, Lappe M, Hoang HD, Gilchrist VH, Hansen AL, Ottosen R, Nielsen CG, Møller C, van der Horst D, Peri S, Balachandran S, Huang J, Jakobsen M, Svenningsen EB, Poulsen TB, Bartsch L, Thielke AL, Luo Y, Alain T, Rehwinkel J, Alcamí A, Hiscott J, Mogensen TH, Paludan SR, and Holm CK

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020
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3. SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate.

Author

Olagnier D, Farahani E, Thyrsted J, Blay-Cadanet J, Herengt A, Idorn M, Hait A, Hernaez B, Knudsen A, Iversen MB, Schilling M, Jørgensen SE, Thomsen M, Reinert LS, Lappe M, Hoang HD, Gilchrist VH, Hansen AL, Ottosen R, Nielsen CG, Møller C, van der Horst D, Peri S, Balachandran S, Huang J, Jakobsen M, Svenningsen EB, Poulsen TB, Bartsch L, Thielke AL, Luo Y, Alain T, Rehwinkel J, Alcamí A, Hiscott J, Mogensen TH, Paludan SR, and Holm CK

Subjects
Adult, Antioxidants pharmacology, Betacoronavirus metabolism, COVID-19, Coronavirus Infections virology, Dimethyl Fumarate pharmacology, Female, Gene Expression, Gene Knockdown Techniques, Humans, Interferon Type I, Lung pathology, Male, NF-E2-Related Factor 2 genetics, Pandemics, Pneumonia, Viral virology, SARS-CoV-2, Signal Transduction drug effects, Succinates pharmacology, Virus Replication drug effects, Anti-Inflammatory Agents pharmacology, Antiviral Agents pharmacology, Betacoronavirus drug effects, Coronavirus Infections drug therapy, Dimethyl Fumarate agonists, NF-E2-Related Factor 2 metabolism, Pneumonia, Viral drug therapy, Succinates agonists
Abstract

Antiviral strategies to inhibit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here, we demonstrate that the NRF2 antioxidant gene expression pathway is suppressed in biopsies obtained from COVID-19 patients. Further, we uncover that NRF2 agonists 4-octyl-itaconate (4-OI) and the clinically approved dimethyl fumarate (DMF) induce a cellular antiviral program that potently inhibits replication of SARS-CoV2 across cell lines. The inhibitory effect of 4-OI and DMF extends to the replication of several other pathogenic viruses including Herpes Simplex Virus-1 and-2, Vaccinia virus, and Zika virus through a type I interferon (IFN)-independent mechanism. In addition, 4-OI and DMF limit host inflammatory responses to SARS-CoV2 infection associated with airway COVID-19 pathology. In conclusion, NRF2 agonists 4-OI and DMF induce a distinct IFN-independent antiviral program that is broadly effective in limiting virus replication and in suppressing the pro-inflammatory responses of human pathogenic viruses, including SARS-CoV2.

Published
2020
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