Nrf2 Signaling in Viral Infections

Reactive oxygen species (Apex, N.C.) Pub Date : 2022-03-03 DOI:10.20455/ros.2022.n.805

E. Ros

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Abstract

Nrf2 is a central regulator of cellular antioxidant and other cytoprotective genes. Several recent studies revealed a novel role for Nrf2 signaling in protecting against viral infections, including COVID-19. The findings from these studies pointed to a feasibility for treating viral infections, including COVID-19, via pharmacological activation of the Nrf2 signaling pathway. (First online: March 3, 2022) REFERENCES Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 1997; 236(2):313–22. doi: https://dx.doi.org/10.1006/bbrc.1997.6943 Yamamoto M, Kensler TW, Motohashi H. The KEAP1-NRF2 system: a thiol-based sensor-effector apparatus for maintaining redox homeostasis. Physiol Rev 2018; 98(3):1169–203. doi: https://dx.doi.org/10.1152/physrev.00023.2017 Kobayashi EH, Suzuki T, Funayama R, Nagashima T, Hayashi M, Sekine H, et al. Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat Commun 2016; 7:11624. doi: https://dx.doi.org/10.1038/ncomms11624 Rojo de la Vega M, Chapman E, Zhang DD. NRF2 and the hallmarks of cancer. Cancer Cell 2018; 34(1):21–43. doi: https://dx.doi.org/10.1016/j.ccell.2018.03.022 Cho HY, Imani F, Miller-DeGraff L, Walters D, Melendi GA, Yamamoto M, et al. Antiviral activity of Nrf2 in a murine model of respiratory syncytial virus disease. Am J Respir Crit Care Med 2009; 179(2):138–50. doi: https://dx.doi.org/10.1164/rccm.200804-535OC Ferrari M, Zevini A, Palermo E, Muscolini M, Alexandridi M, Etna MP, et al. Dengue virus targets Nrf2 for NS2B3-mediated degradation leading to enhanced oxidative stress and viral replication. J Virol 2020; 94(24). doi: https://dx.doi.org/10.1128/JVI.01551-20 Wyler E, Franke V, Menegatti J, Kocks C, Boltengagen A, Praktiknjo S, et al. Single-cell RNA-sequencing of herpes simplex virus 1-infected cells connects NRF2 activation to an antiviral program. Nat Commun 2019; 10(1):4878. doi: https://dx.doi.org/10.1038/s41467-019-12894-z Olagnier D, Farahani E, Thyrsted J, Blay-Cadanet J, Herengt A, Idorn M, et al. SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate. Nat Commun 2020; 11(1):4938. doi: https://dx.doi.org/10.1038/s41467-020-18764-3

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病毒感染中的Nrf2信号

Nrf2是细胞抗氧化和其他细胞保护基因的中心调节因子。最近的几项研究揭示了Nrf2信号在预防病毒感染(包括COVID-19)方面的新作用。这些研究结果表明，通过药理激活Nrf2信号通路来治疗包括COVID-19在内的病毒感染是可行的。(首次在线:2022年3月3日)参考文献itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y，等。Nrf2/小Maf异源二聚体通过抗氧化反应元件介导II期解毒酶基因的诱导。生物化学，生物物理，1997;236(2): 313 - 22所示。doi: https://dx.doi.org/10.1006/bbrc.1997.6943Yamamoto M, Kensler TW, Motohashi H. KEAP1-NRF2系统:用于维持氧化还原稳态的巯基传感器效应装置。physical Rev 2018;98(3): 1169 - 203。doi: https://dx.doi.org/10.1152/physrev.00023.2017Kobayashi EH, Suzuki T, Funayama R, Nagashima T, Hayashi M, Sekine H，等。Nrf2通过阻断促炎细胞因子转录抑制巨噬细胞炎症反应。学报2016;7:11624。doi: https://dx.doi.org/10.1038/ncomms11624Rojo de la Vega M, Chapman E, Zhang DD. NRF2与癌症的标志。Cancer Cell 2018;34(1): 21-43。doi: https://dx.doi.org/10.1016/j.ccell.2018.03.022Cho HY, Imani F, Miller-DeGraff L, Walters D, Melendi GA, Yamamoto M，等。Nrf2在呼吸道合胞病毒病小鼠模型中的抗病毒活性。[J]呼吸急救医学2009;179(2): 138 - 50。doi: https://dx.doi.org/10.1164/rccm.200804-535OCFerrari M, Zevini A, Palermo E, Muscolini M, Alexandridi M, Etna MP，等。登革病毒靶向Nrf2介导ns2b3介导的降解，导致氧化应激增强和病毒复制。[J];94(24)。[J]李建军，李建军，李建军，等。单纯疱疹病毒1感染细胞的单细胞rna测序将NRF2激活与抗病毒程序联系起来。Nat comm2019;10(1): 4878。doi: https://dx.doi.org/10.1038/s41467-019-12894-zOlagnier D, Farahani E, Thyrsted J, Blay-Cadanet J, Herengt A, Idorn M，等。sars - cov2介导的nrf2信号抑制表明4-辛酯-衣康酸酯和富马酸二甲酯具有有效的抗病毒和抗炎活性。Nat comm 2020;11(1): 4938。doi: https://dx.doi.org/10.1038/s41467 - 020 - 18764 - 3

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Reactive oxygen species (Apex, N.C.)

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