Classification and regulatory interactions of key transcription factors in COVID-19
Ndimo Modipane, Saidon Mbambara, Thato Serite, Mike Sathekge, Mankgopo Kgatle
Frontiers in Cellular and Infection Microbiology, doi:10.3389/fcimb.2025.1645333
SARS-CoV-2, the virus responsible for COVID-19, interferes with the host's transcriptional control systems, triggering widespread disruption of immune regulation and metabolic stability. Key transcription factors (TFs), including AHR, NRF2, NF-kB, IRFs, HIF-1a, PARP, STAT3, ATF3, and PPARg, play crucial roles in inflammation, oxidative stress defence, anti-viral responses, and immunometabolic adaptation. Their activity and interactions are modulated by post-translational modifications (PTMs) such as phosphorylation, SUMOylation, and ubiquitination, which shape COVID-19 progression. Specifically, SUMOylation of PPARg suppresses NF-kB-driven inflammation, though impairment under severe disease amplifies macrophage activation and cytokine release. NRF2 degradation via KEAP1-CUL3-mediated ubiquitination is manipulated by the virus to deregulate oxidative stress responses, while SARS-CoV-2 also modulates NF-kB activity through ubiquitination of viral proteins (e.g., NSP6, ORF7a). Dynamic crosstalk between AHR and NRF2 further illustrates TF duality in detoxification and inflammation, with SUMOylation potentially influencing nuclear retention and transcriptional precision. This review classifies transcription factors into four functional categories: inflammatory regulators, antiviral response mediators, stress and pathogen response elements, and metabolic modulators. It further examines how PTM-driven crosstalk contributes to immune dysregulation. Targeting these transcriptional networks presents promising therapeutic strategies to mitigate hyperinflammation, rebalance immune responses, and enhance clinical outcomes in COVID-19.
Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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References
Ahmed-Hassan, Sisson, Shukla, Wijewantha, Funderburg et al., Innate immune responses to highly pathogenic coronaviruses and other significant respiratory viral infections, Front. Immunol,
doi:10.3389/fimmu.2020.01979Anderson, Carbone, Mazzoccoli, Aryl hydrocarbon receptor role in co-ordinating sars-cov-2 entry and symptomatology: Linking cytotoxicity changes in covid-19 and cancers; modulation by racial discrimination stress, Biol. (Basel),
doi:10.3390/biology9090249Badu, Baniulyte, Sammons, Pager, Activation of ATF3 via the integrated stress response pathway regulates innate immune response to restrict Zika virus, J. Virol,
doi:10.1128/jvi.01055-24Baral, Saini, Kandpal, Kundu, Dixit et al., The interplay of co-infections in shaping COVID-19 severity: Expanding the scope beyond SARS-CoV-2, J. Infect. Public Health,
doi:10.1016/j.jiph.2024.102486Bhalla, Heinzinger, Morenikeji, Marzullo, Thomas et al., Transcriptome Profiling Reveals CD73 and Age-Driven Changes in Neutrophil Responses against Streptococcus pneumoniae, Infect. Immun,
doi:10.1128/IAI.00258-21Bhandari, Khanna, Kaushik, Kuhad, Divulging the intricacies of crosstalk between NF-Kb and Nrf2-Keap1 pathway in neurological complications of COVID-19, Mol. Neurobiol,
doi:10.1007/s12035-021-02344-7Boroujeni, Sekrecka, Antonczyk, Hassani, Sekrecki et al., Dysregulated interferon response and immune hyperactivation in severe COVID-19: targeting STATs as a novel therapeutic strategy, Front. Immunol,
doi:10.3389/fimmu.2022.888897Casper, The crosstalk between Nrf2 and NF-kB pathways in coronary artery disease: Can it be regulated by SIRT6?, Life Sci
Castillo Cabrera, Dang, Graves, Zhang, Torres-Castillo et al., AGC kinase inhibitors regulate STING signaling through SGK-dependent and SGK-independent mechanisms, Cell Chem. Biol,
doi:10.1016/j.chembiol.2023.10.008Chen, Kelley, Goldstein, Role of aging and the immune response to respiratory viral infections: potential implications for COVID-19, J. Immunol,
doi:10.4049/jimmunol.2000380Chen, Khan, Close, Goel, Blum et al., SARS-CoV-2 disrupts proximal elements in the JAK-STAT pathway, J. Virol,
doi:10.1128/JVI.00862-21Chen, King, Tu, Sanchez, Luster et al., The roles of IRF-3 and IRF-7 in innate antiviral immunity against dengue virus, J. Immunol,
doi:10.4049/jimmunol.1300799Cheng, Liu, Li, Sun, Liu et al., Protein posttranslational modification in SARS-CoV-2 and host interaction, Front. Immunol,
doi:10.3389/fimmu.2022.1068449Cheng, Yu, Yan, Lai, Xiang, Hypoxia-inducible factor-1a target genes contribute to retinal neuroprotection, Front. Cell Neurosci,
doi:10.3389/fncel.2017.00020Chiang, Liu, The molecular basis of viral inhibition of IRFand STAT-dependent immune responses, Front. Immunol,
doi:10.3389/fimmu.2018.03086Croasdell, Duffney, Kim, Lacy, Sime et al., PPARg and the innate immune system mediate the resolution of inflammation, PPAR Res,
doi:10.1155/2015/549691Dai, Zhou, Li, Qiu, New Insights into the Crosstalk among the Interferon and Inflammatory Signaling Pathways in Response to Viral Infections: Defense or Homeostasis, Viruses,
doi:10.3390/v14122798De Angelis, Anichini, Palamara, Nencioni, Savellini, Dysregulation of intracellular redox homeostasis by the SARS-CoV-2 ORF6 protein, Virol. J,
doi:10.1186/s12985-023-02208-7De Carvalho, Goncalves-De-Albuquerque, Silva, PPAR gamma: From definition to molecular targets and therapy of lung diseases, Int. J. Mol. Sci,
doi:10.3390/ijms22020805Desterke, Turhan, Bennaceur-Griscelli, Griscelli, PPARg Cistrome repression during activation of lung monocyte-macrophages in severe COVID-19, iScience,
doi:10.1016/j.isci.2020.101611Farooqi, Rakhmetova, Kapanova, Tanbayeva, Mussakhanova et al., Role of ubiquitination and epigenetics in the regulation of AhR signaling in carcinogenesis and metastasis: "Albatross around the neck" or "Blessing in disguise, Cells,
doi:10.3390/cells12192382Farrokhi Yekta, Farahani, Koushki, Amiri-Dashatan, Deciphering the potential role of post-translational modifications of histones in gastrointestinal cancers: a proteomics-based review with therapeutic challenges and opportunities, Front. Oncol,
doi:10.3389/fonc.2024.1481426Feng, Weng, Zhou, Owen, Qin et al., Activation of PPARg by a natural flavonoid modulator, apigenin ameliorates obesity-related inflammation via regulation of macrophage polarization, EBioMedicine,
doi:10.1016/j.ebiom.2016.06.017Fernańdez-De-Las-Peñas, Notarte, Peligro, Velasco, Ocampo et al., Long-COVID symptoms in individuals infected with different SARS-CoV-2 variants of concern: A systematic review of the literature, Viruses,
doi:10.3390/v14122629Frank, Paust, Dynamic natural killer cell and T cell responses to influenza infection, Front. Cell Infect. Microbiol,
doi:10.3389/fcimb.2020.00425Gao, Guo, Yang, Wang, Xia et al., Dissecting the crosstalk between Nrf2 and NF-kB response pathways in drug-induced toxicity, Front. Cell Dev. Biol,
doi:10.3389/fcell.2021.809952Ghisletti, Huang, Ogawa, Pascual, Lin et al., Parallel SUMOylation-dependent pathways mediate gene-and signal-specific transrepression by LXRs and PPARg, Mol. Cell,
doi:10.1016/j.molcel.2006.11.022Glanz, Chakravarty, Varghese, Kottapalli, Fan et al., Transcriptional and non-transcriptional activation, posttranslational modifications, and antiviral functions of interferon regulatory factor 3 and viral antagonism by the SARS-coronavirus, Viruses,
doi:10.3390/v13040575Grivennikov, STAT3, activated downstream of cytokine signaling, influences various cellular processes, including immune suppression, apoptosis, and tissue repairDangerous liaisons: STAT3 and NF-kB collaboration and crosstalk in cancer, Cytokine Growth Factor Rev
Guarnieri, Hypothesis: emerging roles for aryl hydrocarbon receptor in orchestrating CoV-2-related inflammation, Cells,
doi:10.3390/cells11040648Guarnieri, Lie, Albrecht, Hewin, Jurado et al., Mitochondrial antioxidants abate SARS-COV-2 pathology in mice, Proc. Natl. Acad. Sci,
doi:10.1073/pnas.2321972121Gudowska-Sawczuk, Mroczko, The role of nuclear factor kappa B (NF-kB) in development and treatment of COVID-19: review, Int. J. Mol. Sci,
doi:10.3390/ijms23095283Guo, Jin, Chen, Ye, Shen et al., NF-kB in biology and targeted therapy: new insights and translational implications, Signal Transduct. Target Ther,
doi:10.1038/s41392-024-01757-9Guryanova, Maksimova, Azova, Transcription factors and methods for the pharmacological correction of their activity, Int. J. Mol. Sci,
doi:10.3390/ijms26136394Gümüs, Erat, Öztürk, Demir, Koyuncu, Oxidative stress and decreased Nrf2 level in pediatric patients with COVID-19, J. Med. Virol,
doi:10.1002/jmv.27640Hadjadj, Yatim, Barnabei, Corneau, Boussier, None
Hahm, Trifilo, Zuniga, Oldstone, Viruses Evade the Immune System through Type I Interferon-Mediated STAT2-Dependent, but STAT1-Independent, Signaling. Immun,
doi:10.1016/j.immuni.2005.01.005Hamad, Al-Kuraishy, Alexiou, Papadakis, Ahmed et al., SARS-CoV-2 infection and dysregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway, Cell Stress Chaperones,
doi:10.1007/s12192-023-01379-0Hariharan, Hakeem, Radhakrishnan, Reddy, Rela, The role and therapeutic potential of NF-kappa-B pathway in severe COVID-19 patients, Inflammopharmacol,
doi:10.1007/s10787-020-00773-9Harmon, Lam, Glass, PPARs and lipid ligands in inflammation and metabolism, Chem. Rev,
doi:10.1021/cr2001355Hasankhani, Bahrami, Tavakoli-Far, Iranshahi, Ghaemi et al., The role of peroxisome proliferator-activated receptors in the modulation of hyperinflammation induced by SARS-CoV-2 infection: A perspective for COVID-19 therapy, Front. Immunol,
doi:10.3389/fimmu.2023.1127358Hord, Petrulis, Perdew, Subcellular localization of the aryl hydrocarbon receptor is modulated by the immunophilin homolog hepatitis B virus X-associated protein 2 *, J. Biol. Chem,
doi:10.1074/jbc.M006873200Hu, Ivashkiv, Cross-regulation of signaling pathways by interferon-gamma: implications for immune responses and autoimmune diseases, Immunity,
doi:10.1016/j.immuni.2009.09.002Jahani, Dokaneheifard, Mansouri, Hypoxia: A key feature of COVID-19 launching activation of HIF-1 and cytokine storm, J. Inflammation,
doi:10.1186/s12950-020-00263-3Janus, Kus, Vydra, Toma-Jonik, Stokowy et al., HSF1 can prevent inflammation following heat shock by inhibiting the excessive activation of the ATF3 and JUN&FOS genes, Cells,
doi:10.3390/cells11162510Jiang, Zhao, Zhou, Xiang, Gutierrez-Castrellon et al., Inflammatory pathways in COVID-19: Mechanism and therapeutic interventions, MedComm,
doi:10.1002/mco2.154Karki, Sharma, Tuladhar, Williams, Zalduondo et al., Synergism of TNF-a and IFN-g triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes, bioRxiv Prepr. Serv. Biol,
doi:10.1101/2020.10.29.361048Kasembeli, Bharadwaj, Robinson, Tweardy, Contribution of STAT3 to inflammatory and fibrotic diseases and prospects for its targeting for treatment, Int. J. Mol. Sci,
doi:10.3390/ijms19082299Kesika, Thangaleela, Sisubalan, Radha, Sivamaruthi et al., The role of the nuclear factor-kappa B (NF-kB) pathway in SARS-CoV-2 infection, Pathogens,
doi:10.3390/pathogens13020164Kgatle, Lawal, Mashabela, Boshomane, Koatale et al., COVID-19 is a multi-organ aggressor: epigenetic and clinical marks, Front. Immunol,
doi:10.3389/fimmu.2021.752380Kim, Silwal, Peroxisome proliferator-activated receptortargeted therapies: challenges upon infectious diseases, Cells,
doi:10.3390/cells12040650Kobayashi, Suzuki, Funayama, Nagashima, Hayashi et al., Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription, Nat. Commun,
doi:10.1038/ncomms11624Kombe Kombe, Fotooh Abadi, Nanduri, Gerasimova, Daskou et al., The role of the Nrf2 pathway in airway tissue damage due to viral respiratory infections, Int. J. Mol. Sci,
doi:10.3390/ijms25137042Labzin, Schmidt, Masters, Beyer, Krebs et al., ATF3 is a key regulator of macrophage IFN responses, J. Immunol,
doi:10.4049/jimmunol.1500204Lai, Shih, Ko, Tang, Hsueh, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges, Int. J. Antimicrob. Agents,
doi:10.1016/j.ijantimicag.2020.105924Lee, Collaborative power of Nrf2 and PPARg Activators against metabolic and drug-induced oxidative injury, Oxid. Med. Cell Longev,
doi:10.1155/2017/1378175Lee, Oldham, He, Wang, Mulhern et al., Interferon-g Impairs human coronary artery endothelial glucose metabolism by tryptophan catabolism and activates fatty acid oxidation, Circ,
doi:10.1161/CIRCULATIONAHA.121.053960Lee, Park, Jeong, Ahn, Choi et al., Immunophenotyping of covid-19 and influenza highlights the role of type i interferons in development of severe covid-19, Sci. Immunol,
doi:10.1126/sciimmunol.abd1554Lekshmi, Asha, Sanicas, Asi, Arya et al., PI3K/Akt/Nrf2 mediated cellular signaling and virus-host interactions: latest updates on the potential therapeutic management of SARS-CoV-2 infection, Front. Mol. Biosci,
doi:10.3389/fmolb.2023.1158133Li, Jing, Dong, Zhang, Wang, Activating transcription factor 3: A potential therapeutic target for inflammatory pulmonary diseases, Immun. Inflammation Dis,
doi:10.1002/iid3.1028Li, Jing, Dong, Zhang, Wang, Activating transcription factor 3: A potential therapeutic target for inflammatory pulmonary diseases, Immun. Inflammation Dis,
doi:10.1002/iid3.1028Li, Qiao, You, Zong, Peng et al., SARS-CoV-2 Nsp5 activates NF-kB pathway by upregulating SUMOylation of MAVS, Front. Immunol,
doi:10.3389/fimmu.2021.750969Liang, Wang, Yu, Wang, Zhang et al., Transcriptional regulation and small compound targeting of ACE2 in lung epithelial cells, Acta Pharmacol. Sin,
doi:10.1038/s41401-022-00906-6Lin, Heylbroeck, Pitha, Hiscott, Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome-mediated degradation, Mol. Cell Biol,
doi:10.1128/MCB.18.5.2986Liu, Li, Lan, Hao, Baz et al., The dual roles of activating transcription factor 3 (ATF3) in inflammation, apoptosis, ferroptosis, and pathogen infection responses, Int. J. Mol. Sci,
doi:10.3390/ijms25020824Liu, Xiang, Zhang, Yao, Wang, Hypoxia-inducible factor-1: A potential target to treat acute lung injury, Oxid. Med. Cell Longev,
doi:10.1155/2020/8871476Lukhele, Boukhaled, Brooks, Type I interferon signaling, regulation and gene stimulation in chronic virus infection, Semin. Immunol,
doi:10.1016/j.smim.2019.05.001Mackelprang, Filali-Mouhim, Richardson, Lefebvre, Katabira et al., Upregulation of IFN-stimulated genes persists beyond the transitory broad immunologic changes of acute HIV-1 infection, iScience,
doi:10.1016/j.isci.2023.106454Mahjoor, Mahmoudvand, Farokhi, Shadab, Kashfi et al., Double-edged sword of JAK/STAT signaling pathway in viral infections: novel insights into virotherapy, Cell Commun. Signal,
doi:10.1186/s12964-023-01240-yMajidpoor, Mortezaee, Interleukin-6 in SARS-CoV-2 induced disease: Interactions and therapeutic applications, BioMed. Pharmacother,
doi:10.1016/j.biopha.2021.112419Mittal, Siddiqui, Tran, Reddy, Malik, Reactive oxygen species in inflammation and tissue injury, Antioxid. Redox Signal,
doi:10.1089/ars.2012.5149Mokuda, Tokunaga, Masumoto, Sugiyama, Angiotensinconverting enzyme 2, a SARS-CoV-2 receptor, is upregulated by interleukin 6 through STAT3 signaling in synovial tissues, J. Rheumatol,
doi:10.3899/jrheum.200547Moon, Cho, Jhun, Choi, Na et al., Small heterodimer partner-interacting leucine zipper protein suppresses pain and cartilage destruction in an osteoarthritis model by modulating the AMPK/STAT3 signaling pathway, Arthritis Res. Ther,
doi:10.1186/s13075-024-03417-3Morris, Kershaw, Babon, The molecular details of cytokine signaling via the JAK/STAT pathway, Protein Sci,
doi:10.1002/pro.3519Muchtaridi, Amirah, Harmonis, Ikram, Role of nuclear factor erythroid 2 (Nrf2) in the recovery of long COVID-19 using natural antioxidants: A systematic review, Antioxid. MDPI,
doi:10.3390/antiox11081551Ngo, Duennwald, Nrf2 and oxidative stress: A general overview of mechanisms and implications in human disease, Antioxid,
doi:10.3390/antiox11122345Ning, Huye, Pagano, Regulation of the transcriptional activity of the IRF7 promoter by a pathway independent of interferon signaling*, J. Biol. Chem
Nishitsuji, Iwahori, Ohmori, Shimotohno, Murata, Ubiquitination of SARS-CoV-2 NSP6 and ORF7a facilitates NF-kB activation, MBio,
doi:10.1128/mbio.00971-22Noel, Martina, Bandapalle, Racusen, Potteti et al., T lymphocyte-specific activation of Nrf2 protects from AKI, J. Am. Soc. Nephrol,
doi:10.1681/ASN.2014100978Park, Rustamov, Roh, The roles of NFR2-regulated oxidative stress and mitochondrial quality control in chronic liver diseases, Antioxid,
doi:10.3390/antiox12111928Pauciullo, Riccio, Santopolo, Albecka, Papa et al., Human coronaviruses activate and hijack the host transcription factor HSF1 to enhance viral replication, Cell Mol. Life Sci,
doi:10.1007/s00018-024-05370-5Piaszyk-Borychowska, Szeĺes, Csermely, Chiang, Wesoły et al., Signal integration of IFN-I and IFN-II with TLR4 involves sequential recruitment of STAT1-Complexes and NFkB to enhance pro-inflammatory transcription, Front. Immunol,
doi:10.3389/fimmu.2019.01253Pietrobon, Teixeira, Sato, Immunosenescence and inflammaging: risk factors of severe COVID-19 in older people, Front. Immunol,
doi:10.3389/fimmu.2020.579220Qiao, Giannopoulou, Chan, Park, Gong et al., Synergistic activation of inflammatory cytokine genes by interferon-g-induced chromatin remodeling and toll-like receptor signaling, Immunity,
doi:10.1016/j.immuni.2013.08.009Qu, Haas De Mello, Morris, Jones-Hall, Ivanciuc et al., SARS-coV-2 inhibits NRF2-mediated antioxidant responses in airway epithelial cells and in the lung of a murine model of infection, Microbiol. Spectr,
doi:10.1128/spectrum.00378-23Ramakrishnan, Anand, Roy, Vascular endothelial growth factor signaling in hypoxia and inflammation, J. Neuroimmune Pharmacol. Off J. Soc. NeuroImmune Pharmacol,
doi:10.1007/s11481-014-9531-7Ramazi, Allahverdi, Zahiri, Evaluation of post-translational modifications in histone proteins: A review on histone modification defects in developmental and neurological disorders, J. Biosci,
doi:10.1007/s12038-020-00099-2Rebe, Veǵran, Berger, Ghiringhelli, STAT3 activation: A key factor in tumor immunoescape, JAK-STAT,
doi:10.4161/jkst.23010Ren, Ji, Huang, Aniagu, Jiang et al., AHR-mediated ROS production contributes to the cardiac developmental toxicity of PM2.5 in zebrafish embryos, Sci. Total Environ
Riedl, Faure-Dupuy, Rolland, Schuehle, Hizir et al., Hypoxia-inducible factor 1 alpha-mediated RelB/APOBEC3B down-regulation allows hepatitis B virus persistence, Hepatol
Rincon-Arevalo, Aue, Ritter, Szelinski, Khadzhynov et al., Altered increase in STAT1 expression and phosphorylation in severe COVID-19, Eur. J. Immunol,
doi:10.1002/eji.202149575Rodriguez, Carnevale, Systematic review: JAK-STAT regulation and its impact on inflammation response in ARDS from COVID-19, Immuno,
doi:10.3390/immuno4020010Ruan, Zhang, Zhang, Li, Ran, Unraveling the role of HIF-1a in sepsis: from pathophysiology to potential therapeutics-a narrative review, Crit. Care,
doi:10.1186/s13054-024-04885-4Rudiansyah, Jasim, Mohammad Pour, Athar, Jeda et al., Coronavirus disease 2019 (COVID-19) update: From metabolic reprogramming to immunometabolism, J. Med. Virol,
doi:10.1002/jmv.27929Salem, Li, Hindi, Casablanca, Zhong et al., Activation of STAT3 signaling pathway in the kidney of COVID-19 patients, J. Nephrol,
doi:10.1007/s40620-021-01173-0Santoni, Ghosh, Derelitto, Saha, Transcription factor driven gene regulation in COVID-19 patients, Viruses,
doi:10.3390/v15051188Sayahinouri, Mashayekhi Firouz, Ebrahimi Sadrabadi, Masoudnia, Abdolahi et al., Functionality of immune cells in COVID-19 infection: development of cell-based therapeutics, Bioimpacts,
doi:10.34172/bi.2023.23839Schmitz, Shaban, Albert, Gökcȩn, Kracht, The crosstalk of Endoplasmic Reticulum (ER) stress pathways with NF-kB: Complex mechanisms relevant for cancer, inflammation and infection, Biomedicines,
doi:10.3390/biomedicines6020058Serebrovska, Chong, Serebrovska, Tumanovska, Xi, Hypoxia, HIF-1a, and COVID-19: from pathogenic factors to potential therapeutic targets, Acta Pharmacol. Sin,
doi:10.1038/s41401-020-00554-8Shi, Serine/Threonine Phosphatases: Mechanism through Structure, Cell
Shouman, El-Kholy, Hussien, El-Derby, Magdy et al., SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147, Cell Commun. Signal,
doi:10.1186/s12964-024-01718-3Snyder, Huang, Huang, Zhang, A signal transducer and activator of transcription 3•Nuclear factor kB (Stat3•NFkB) complex is necessary for the expression of fascin in metastatic breast cancer cells in response to interleukin (IL)-6 and tumor necrosis factor (TNF)-a*, J. Biol. Chem,
doi:10.1074/jbc.M114.591719Song, Li, Xie, Hou, You, Cytokine storm induced by SARS-CoV-2, Clin. Chim. Acta
Sood, Sharma, Vishal, Saha, Dhapola et al., ATF3 negatively regulates cellular antiviral signaling and autophagy in the absence of type I interferons, Sci. Rep,
doi:10.1038/s41598-017-08584-9Tang, Wang, Wang, Huang, Xu, Emerging role of hypoxia-inducible factor-1a in inflammatory autoimmune diseases: A comprehensive review, Front. Immunol,
doi:10.3389/fimmu.2022.1073971Theodore, Kawai, Yang, Kleshchenko, Reddy et al., Multiple nuclear localization signals function in the nuclear import of the transcription factor Nrf2*, J. Biol. Chem
Tian, Liu, Li, Zhao, Shereen et al., HIF-1a promotes SARS-CoV-2 infection and aggravates inflammatory responses to COVID-19, Signal Transduct. Target Ther,
doi:10.1038/s41392-021-00726-wTrikha, Lee, The role of AhR in transcriptional regulation of immune cell development and function, Biochim. Biophys. Acta -Rev. Cancer,
doi:10.1016/j.bbcan.2019.188335Turski, Wnorowski, Turski, Turski, Turski, AhR and IDO1 in pathogenesis of Covid-19 and the "Systemic AhR Activation Syndrome:" a translational review and therapeutic perspectives, Restor. Neurol. Neurosci,
doi:10.3233/RNN-201042Van Avondt, Strecker, Tulotta, Minnerup, Schulz et al., Neutrophils in aging and aging-related pathologies, Immunol. Rev,
doi:10.1111/imr.13153Van Uden, Kenneth, Rocha, Regulation of hypoxia-inducible factor-1alpha by NF-kappaB, Biochem. J,
doi:10.1042/BJ20080476Varga, Czimmerer, Nagy, PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation, Biochim. Biophys. Acta -Mol. Basis Dis
Vaźquez-Jimeńez, Avila-Ponce De Leoń, Matadamas-Guzman, Muciño-Olmos, Martıńez-Loṕez et al., On deep landscape exploration of COVID-19 patients cells and severity markers, Front. Immunol,
doi:10.3389/fimmu.2021.705646Wakabayashi, Slocum, Skoko, Shin, Kensler, When NRF2 talks, who's listening?, Antioxid. Redox Signal,
doi:10.1089/ars.2010.3216Wang, Liang, Zen, Molecular mechanisms that influence the macrophage M1-M2 polarization balance, Front. Immunol,
doi:10.3389/fimmu.2014.00614Wang, Vadakke-Madathil, Croft, Brody, Chaudhry, HIF1alpha cardioprotection in COVID-19 patients, medRxiv
Wardyn, Ponsford, Sanderson, Dissecting molecular cross-talk between Nrf2 and NF-kB response pathways, Biochem. Soc. Trans,
doi:10.1042/BST20150014Wei, Yang, Wu, Zhao, Mu et al., Immune imprinting blunts omicron pathogenicity fluctuations and highlights the essential role of cellular immunity in SARS-CoV-2 infection, Cell Rep,
doi:10.1016/j.celrep.2025.115784Woodall, Cujba, Worlock, Case, Masonou et al., Age-specific nasal epithelial responses to SARS-CoV-2 infection, Nat. Microbiol,
doi:10.1038/s41564-024-01658-1Wu, Metcalf, The role of type I IFNs in influenza: antiviral superheroes or immunopathogenic villains?, J. Innate Immun,
doi:10.1159/000508379Xing, Bi, Chang, Zang, Wang et al., SUMOylation of AhR modulates its activity and stability through inhibiting its ubiquitination, J. Cell Physiol,
doi:10.1002/jcp.24092Yan, Gibson, Buckley, Qin, Benveniste, Role of the JAK/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases, Clin. Immunol,
doi:10.1016/j.clim.2016.09.014Yu, Zuo, Cai, Huang, Wu et al., SENP1 regulates IFN-g-STAT1 signaling through STAT3-SOCS3 negative feedback loop, J. Mol. Cell Biol,
doi:10.1093/jmcb/mjw042Zhai, Franco, Atmar, Quarles, Arden et al., Host transcriptional response to influenza and other acute respiratory viral infections -A prospective cohort study, PloS Pathog,
doi:10.1371/journal.ppat.1004869Zhang, Chen, Tian, Fu, Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects, Front. Cell Infect. Microbiol,
doi:10.3389/fcimb.2024.1407261Zhang, Hu, Yang, Zhang, Zhang et al., Interaction between AhR and HIF-1 signaling pathways mediated by ARNT/HIF-1b, BMC Pharmacol. Toxicol,
doi:10.1186/s40360-022-00564-8Zhang, Liu, Hu, Chen, Yuan, Hyperactivated IRF-1 and STAT1 contribute to enhanced Interferon stimulated gene (ISG) expression by Interferon a and g co-treatment in human hepatoma cells, Biochim. Biophys. Acta -Gene Struct. Expr
Zhang, Shang, Fan, Gu, Xu et al., The efficacy and safety of janus kinase inhibitors for patients with COVID-19: A living systematic review and meta-analysis, Front. Med,
doi:10.3389/fmed.2021.800492Zhang, Wei, Wang, Liu, Hou et al., NF-kB activation enhances STING signaling by altering microtubule-mediated STING trafficking, Cell Rep,
doi:10.1016/j.celrep.2023.112185Zhong, Xiao, Qiu, Xu, Chen et al., Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications, MedComm,
doi:10.1002/mco2.261Zhou, Zhang, Dong, Wang, Zhang et al., The role of SARS-CoV-2-mediated NF-kB activation in COVID-19 patients, Hypertens. Res,
doi:10.1038/s41440-023-01460-2Znaidia, Demeret, Van Der Werf, Komarova, Characterization of SARS-CoV-2 evasion: interferon pathway and therapeutic options, Viruses,
doi:10.3390/v14061247Øvrevik, Låg, Lecureur, Gilot, Lagadic-Gossmann et al., AhR and Arnt differentially regulate NF-kB signaling and chemokine responses in human bronchial epithelial cells, Cell Commun. Signal,
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"abstract": "<jats:p>SARS-CoV-2, the virus responsible for COVID-19, interferes with the host’s transcriptional control systems, triggering widespread disruption of immune regulation and metabolic stability. Key transcription factors (TFs), including AHR, NRF2, NF-κB, IRFs, HIF-1α, PARP, STAT3, ATF3, and PPARγ, play crucial roles in inflammation, oxidative stress defence, anti-viral responses, and immunometabolic adaptation. Their activity and interactions are modulated by post-translational modifications (PTMs) such as phosphorylation, SUMOylation, and ubiquitination, which shape COVID-19 progression. Specifically, SUMOylation of PPARγ suppresses NF-κB-driven inflammation, though impairment under severe disease amplifies macrophage activation and cytokine release. NRF2 degradation via KEAP1–CUL3–mediated ubiquitination is manipulated by the virus to deregulate oxidative stress responses, while SARS-CoV-2 also modulates NF-κB activity through ubiquitination of viral proteins (e.g., NSP6, ORF7a). Dynamic crosstalk between AHR and NRF2 further illustrates TF duality in detoxification and inflammation, with SUMOylation potentially influencing nuclear retention and transcriptional precision. This review classifies transcription factors into four functional categories: inflammatory regulators, antiviral response mediators, stress and pathogen response elements, and metabolic modulators. It further examines how PTM–driven crosstalk contributes to immune dysregulation. Targeting these transcriptional networks presents promising therapeutic strategies to mitigate hyperinflammation, rebalance immune responses, and enhance clinical outcomes in COVID-19.</jats:p>",
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"author": "Moon",
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"DOI": "10.3390/antiox11081551",
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"author": "Ning",
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"DOI": "10.1016/j.immuni.2013.08.009",
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