Oxidative Medicine and Cellular Longevity / 2018 / Article / Tab 1

Review Article

Therapeutic Modulation of Virus-Induced Oxidative Stress via the Nrf2-Dependent Antioxidative Pathway

Table 1

Summary of positive and negative regulations of the Nrf2 pathway by various pathogenic viruses.

VirusDiseaseHost cells or animalsViral ROS inducerROS levelEffect on redox defense systemEffect on Nrf2Effect on Nrf2 target genesEffect on othersReference

MoMuLV ts1Neurodegenerative diseaseImmortalized astrocytesgPr80envH2O2GSH↑, cysteine↑, γ-GT↑, CAT↑xCT↑, GCLC↑, GCLM↑, GPx↑Sensitivity to cystine deprivation↑, Bcl-2↑, xCT antiporter↑, GRP78↑, GRP94↑, CalR↑Qiang et al. [58]

HIVNeurodegenerative diseaseAstrocytesgp120NDNQO1↑, HO-1↑Ca2+Reddy et al. [8, 9]
Neurocognitive disorderHuman neuroblastoma cellsTatH2O2NDNQO1↑, CAT↑, SOD1↑, SOD2↑, HO-1↑NMDA receptor↑, SMO↑, spermidine↑Mastrantonio et al. [65]
AIDSHeLa-CD4-LTR-β-galactosidase cellsTatGSH↓NQO1↑, HO-1↑, AKR1C1↑Tat-induced LTR transactivation↓, NF-κB↑Zhang et al. [63], Zhang et al. [64]
Respiratory disorderAlveolar epithelial cellsgp120, TatGSH↓NDTER↓Fan et al. [51]
Respiratory disorderMonocyte-derived macrophagesgp120, TatNDNDNQO1↓, GCLC↓H2O2 scavenging↓, phagocytosis↓Staitieh et al. [53]
AIDSTransgenic ratsgp120, TatNDHO-1↓Senescence↑Davinelli et al. [50]

HCVViral hepatitisHepatoma cellsNDNDNDPhosphorylation↑NQO1↑, HO-1↑, GCL↑p38↑, JNK↑, phospho-Bad↑, phospho-Akt↑Burdette et al. [48]
Viral hepatitisHepatoma cellsCore, NS5ANDNuclear localization↑HO-1↑, NQO1↑PKC↑, CK2↑, PI-3K↑Ivanov et al., 2011; Smirnova et al., 2016
Viral hepatitisPersistently infected hepatoma cellsNDNDNDPhosphorylation↑, nuclear localization↑NQO1↑, GCLC↑, Maf G↑, G6PD↑, MTHFD2↑, ASNS↑LD↑, cholesterol↑, triacylglycerol↑Sugiyama et al. [77]
HCCHepatoma cellsNDNDGSH↑PGD↑, GCLC↑, NQO1↑, UGDH↑Tolerance to anticancer drug↑, phospho-p62↑, interaction with KEAP1↑Saito et al. [78]; Medvedev et al., 2017
Viral hepatitisHepatoma cellsCore, NS3NDNQO1↓, GCLC↓, GPx↓sMaf↑, sMaf delocalization↑, proteasomal activity↓, PSMB5↓, sMaf-NS3 interaction↑Carvajal-Yepes et al. [49]

Influenza virusRespiratory diseaseHuman primary alveolar type I-like cellsNDNDNuclear localization↑HO-1↑Caspase 1↑, caspase 3↑, IL-8↑Kosmider et al. [44]
Respiratory diseaseHuman bronchial adenocarcinoma cellsNDNDPhosphorylation↓NDFibronectin↓Simon et al. [84]

RSVRespiratory diseaseHuman alveolar type II-like epithelial cells and small airway epithelial cellsNDGSH↓SOD1↓, SOD2↑, SOD3↓, GST↓, CAT↓, GPx↓F2-isoprostane↑, NOX↑, RANTES↑, IL-8↑Hosakote et al., 2009
Respiratory diseaseNrf2(+/+) miceNDNDNuclear ARE binding↑↓GCLC↑↓, UGT1↑↓, NQO1↑↓, HO-1↑↓, GST↑↓, GPx↑↓NDCho et al. [19]
Respiratory diseaseMurine bronchoalveolar lavage, patient samplesNDGSH↓Nuclear form↓SOD1↓, SOD3↓, CAT↓, GST↓, GPx↓F2-isoprostane↑, MDA↑Hosakote et al. [20], Komaravelli and Casola [89]
Respiratory diseaseHuman bronchial epithelial cellsNDNDNDHO-1↓, GPx↓ICAM-1↑, b-tubulin↓, Foxj1↓, Dnai2↓, MUC5AC↑, hCLCA1↑, IL-13↑, IL-8↑, IL-6↑, TNF-αMata et al. [88]
Respiratory diseaseHuman alveolar type II-like epithelial cells (A549) and small airway epithelial cellsNDNDNQO1↓, CAT↓, SOD1↓CBP↓, HDAC1↑, HDAC2↑Komaravelli et al. [90]
Respiratory diseaseHuman alveolar type II-like epithelial cells and small airway epithelial cellsNDNDNDCAT↓, SOD1↓Nrf2-SUMO2/3↑, PML↑, Nrf2-PML↑Komaravelli et al. [43]

HBVViral hepatitisHepG2.2.15, HepAD38HBx and LHBs8-OHdG↓, DNPH↓NQO1↑, GPx↑, GCL↑c-Raf↑, constitutive proteasome↑, immunoproteasome↓, Mafs↓Schaedler et al. [99]
Viral hepatitisHepG2 cellsHBxNDHO-1↑, NQO1↑p-ATM↑, p-Chk2↑, PKC-d↑Matsuda et al. [100]
Viral hepatitisHepG2, HepG2.2.15, Huh7HBxNDNDG6PD↑, NQO1↑, GST↑, Cyp2a5↑p62-KEAP1↑, immobilized KEAP1↑, cell proliferation↑Liu et al. [46]
Viral hepatitisHepG2, Huh7.5, HepAD38, HBV transgenic miceNDNDNDNQO1↑, GCLC↑, HBsAg↑PCNA↓, insulin receptor inside↑, insulin receptor surface↓, ALT↑, AST↑, insulin binding↓, α-taxillin↑, insulin response↓Barthel et al. [101]
Viral hepatitisHuh7.5 and HepG2HBsAgNDNQO1↓, AP1↓, GPx↓HBsAg↓, HBeAg↓, subviral particles accumulate at ER due to preS1preS2 domainPeiffer et al. [52]

HSVEncephalitis-associated neurotoxicityHerpes encephalitic mice, microglial cellsNDGSH↓HO-1↑, GPx↑NDSchachtele et al. [105]

HCMVCongenital abnormalitiesHuman foreskin fibroblastsNDNDGSH↑SOD↑, GPx↑, GCLC↑, HO-1↑, NQO1↑Maintenance of mTOR activityTilton et al. [106]
Congenital abnormalitiesPrimary human foreskin fibroblastsViral gene productsNDHO-1↑, GCLC↑IE1↑, IE2↑, CK2↑, cell viability↑, GSH↑Lee et al. [11, 42]

KSHVSarcomaHuman dermal microvascular endothelial cellsORF71, vFLIPNDNuclear localization↑HO-1↑, NQO1↑, GCL↑LANA-1↑, Src↑, PKC↑, VEGF↑, COX-2↑, PGE2↑, LANA1-Nrf2↑, KEAP1-Nrf2↑Gjyshi et al. [45]

DENVFeverMonocyte-derived dendritic cellNDHO-1↑, NQO1↑, SOD2↑, GCLM↑, GCLC↑IRF3↑, STAT1↑, RIG-I↑, IFIT1↑, LANA-1↑, NOX↑, TNF-α, IL-6↑, IFN-β1↑, ISG↑, annexin V↑Olagnier et al. [39]
FeverMononuclear phagocytesNS2B3NDNDCLEC5A↑, TNF-α↑, ER stress↑, PERK↑Cheng et al. [47]

Marburg virusHemorrhagic fever293T, Huh7, and Vero E6 cellsVP24NDNDNuclear localization↑HO-1↑, NQO1↑, GCLM↑VP24-KEAP1 Kelch domain interaction↑, VP24-KEAP1 mislocalizationPage et al. [113], Edwards et al. [112]
Hemorrhagic feverHuman monocytic cellsVP24NDNDNDVP24 dimmerization↓, VP24 monomer cysteines-KEAP1↑Johnson et al. [114]

SVCVSpring viremiaEpithelioma papulosum cyprini cellsNDNDHO-1↑, SOD1↑8-OHdG↑, FRAP↑Yang et al. [117], Shao et al. [116]

WNVArboviral encephalitisBHK cellsNDGSH↑GCLC↑, SOD↑, GPx↑Arsenite-induced stress granule↓, ATF4↑, arsenite-induced mitochondrial damage↓, mitochondrial morphology change↑Basu et al. [121]

RGNNVFish diseaseThe grouper fin cellsNDSOD↑, CAT↑SOD↑, CAT↑Apoptosis↑, mitochondrial potential↓Chang et al. [123]

Virus names, diseases caused by viruses, host cells or animals used for infection, ROS level after infection, effect on the redox defense system, effect on Nrf2 and its target genes, and other effects were listed accordingly. ND indicates “not determined.” Abbreviations used within the table are as follows. 8-OHdG: 8-hydroxydeoxyguanosine; AIDS: acquired immunodeficiency syndrome; AKR1C: aldo-ketoreductase 1C1; Akt: protein kinase B; ALT: alanine aminotransferase; AP-1: transcription factor composed of cFos and cJun dimer; ARE: antioxidant response element; ASNS: asparagine synthetase; AST: aspartate aminotransferase; ATM: ATM serine/threonine inase; Bad: bcl-2-associated death promoter; Bcl-2: B-cell lymphoma 2; CalR: calreticulin; CAT: catalase; CBP: CREB-binding protein; Chk2: checkpoint kinase 2; CK2: casein kinase 2; CLEC5A: c-type lectin domain family 5, member A; COX-2: cyclooxygenase 2; c-Raf: RAF protooncogene serine/threonine-protein kinase; Cyp2a5: cytochrome P450 2A5; DENV: dengue virus; Dnai2: dynein intermediate chain 2; DNPH: 2,4-dinitrophenylhydrazine; Foxj1: forkhead box protein J1; FRAP: ferric reducing ability of plasma reagent; G6PD: glucose 6 phosphate dehydrogenase; GCLC: glutamate cysteine ligase catalytic subunit; GCLM: glutamate cysteine ligase regulatory subunit; γ-GT: gamma-glutamyl transpeptidase; GPx: glutathione peroxidase; GRP78: glucose-responsive proteins 78; GRP94: glucose-responsive proteins 94; GSH: glutathione; GST: glutathione S transferase; HBeAg: hepatitis B e antigen; HBsAg: hepatitis B surface antigen; HBx: hepatitis B virus protein X; HCC: hepatocellular carcinoma; hCLCA1: human chloride channel accessory 1; HCMV: human cytomegalovirus; HCV: hepatitis C virus; HDAC: histone deacetylase; HIV: human immunodeficiency virus; HO-1: heme oxygenase; HSV: herpes simplex virus; ICAM-1: intercellular adhesion molecule 1; IE1: immediate early protein 1; IE2: immediate early protein 2; IFIT1: interferon-induced protein with tetra-tricopeptide repeats 1; IFN: interferon; IL-13: interleukin 13; IL-6: interleukin 6; IL-8: interleukin 8; IRF: IFN regulatory factor 3; ISG: interferon-stimulated gene; JNK: c-Jun kinase; KEAP1: Kelch-like ECH-associated protein 1; KSHV: Kaposi’s sarcoma-associated herpesvirus; LANA-1: latency-associated nuclear antigen 1; LD: lipid droplet; LHBs: hepatitis B virus large surface protein; LTR: long terminal repeat; Maf: transcription factor Maf; MDA: malondialdehyde; MoMuLV ts1: Moloney murine leukemia virus ts1; MTHFD2: methylenetetrahydrofolate dehydrogenase 2; mTOR: mammalian target of rapamycin; MUC5AC: mucin 5AC; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; NMDA: N-methyl-D-aspartate; NOX: NADPH oxidase; NQO1: NAD(P)H dehydrogenase quinone 1; NS2B3: nonstructural protein 2B3; NS3: nonstructural protein 3; NS5A: nonstructural protein 5A; ORF71: open reading frame 71; PCNA: proliferating cell nuclear antigen; PERK: protein kinase R-like ER kinase; PGD: phosphogluconate dehydrogenase; PGE2: prostaglandin E2; PI3K: phosphatidyl inositol 3 kinase; PKC: protein kinase C; PML: promyelocytic leukemia protein; PSMB5: proteasome subunit beta type-5; RANTES: regulated on activation, normal T cell expressed and secreted; RGNNV: red-spotted grouper nervous necrosis virus; RIG-I: RIG-I-like receptor; RSV: respiratory syncytial virus; sMaf: small musculoaponeurotic fibrosarcoma; SMO: spermine oxidase; SOD: superoxide dismutase; Src: protooncogene tyrosine-protein kinase; STAT1: signal transducer and activator of transcription 1; SUMO: small ubiquitin-like modifier; SVCV: spring viremia of carp virus; TER: transepithelial electrical resistance; TNF-α: tumor necrosis factor alpha; UGDH: UDP-glucose dehydrogenase; VEGF: vascular endothelial growth factor; vFLIP: viral FLICE-like inhibitory protein; WNV: West Nile virus; xCT: cell surface cysteine-glutamate antiporter.

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