KEGG   PATHWAY: emc05168
Entry
emc05168                    Pathway                                
Name
Herpes simplex virus 1 infection - Eublepharis macularius (Leopard gecko)
Description
Herpes simplex virus 1(HSV-1) is a common human pathogen, which initially infects orofacial mucosal surfaces. The virus replicates in epithelial cells at these sites, causing clinically overt disease characterized by vesicular lesions. HSV-1 then penetrates to the nervous system and establishes latency in sensory neurons. Throughout the lifetime of the host, HSV-1 may reactivate from its latent state and reinitiate a lytic infection cycle. HSV-1 has developed various mechanisms to escape its host innate immune responses and increased its capacity to replicate and to persist. ICP34.5, ICP0, ICP27, Us11 and Vhs (UL41) are the proteins involved in viral interference.
Class
Human Diseases; Infectious disease: viral
Pathway map
emc05168  Herpes simplex virus 1 infection
emc05168

Disease
H00365  Herpes simplex virus infection
Organism
Eublepharis macularius (Leopard gecko) [GN:emc]
Gene
129323647  EIF2B2; translation initiation factor eIF-2B subunit beta [KO:K03754]
129323679  FADD; LOW QUALITY PROTEIN: FAS-associated death domain protein [KO:K02373]
129323728  IFNGR1; interferon gamma receptor 1 [KO:K05132]
129323779  [KO:K12893]
129323801  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
129323844  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
129323951  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
129323978  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129324134  SRSF5; serine/arginine-rich splicing factor 5 isoform X1 [KO:K12893]
129324533  [KO:K08738]
129324633  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
129324796  IRF7; interferon regulatory factor 7 [KO:K09447]
129324997  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
129325086  IFIH1; interferon-induced helicase C domain-containing protein 1 [KO:K12647] [EC:5.6.2.6]
129325143  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
129325489  IFNGR2; interferon gamma receptor 2 [KO:K05133]
129325744  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
129325802  [KO:K16060]
129325815  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
129325820  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
129326227  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
129326507  POU2F1; POU domain, class 2, transcription factor 1 [KO:K09364]
129327021  [KO:K06752]
129327024  [KO:K06752]
129327209  [KO:K06751]
129327210  [KO:K06751]
129327212  [KO:K06751]
129327434  [KO:K06752]
129327479  CD74; HLA class II histocompatibility antigen gamma chain [KO:K06505]
129327588  IL12B; interleukin-12 subunit beta [KO:K05425]
129327984  [KO:K06752]
129328039  [KO:K06752]
129328040  [KO:K06752]
129328041  [KO:K06752]
129328043  [KO:K06752]
129328044  [KO:K06752]
129328045  [KO:K06752]
129328133  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
129328259  ALYREF; THO complex subunit 4 [KO:K12881]
129328279  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
129328280  SRSF2; serine/arginine-rich splicing factor 2 [KO:K12891]
129328323  DAXX; LOW QUALITY PROTEIN: death domain-associated protein 6 [KO:K02308]
129328479  [KO:K06751]
129328487  [KO:K06752]
129328493  [KO:K06752]
129328494  [KO:K06752]
129328495  [KO:K06752]
129328497  [KO:K06752]
129328498  [KO:K06752]
129328499  [KO:K06752]
129328500  [KO:K06752]
129328502  [KO:K06752]
129328503  [KO:K06752]
129328504  [KO:K06752]
129328506  [KO:K06752]
129328507  [KO:K06752]
129328508  [KO:K06752]
129328509  [KO:K06752]
129328511  [KO:K06752]
129328742  [KO:K08058]
129328847  TNF; tumor necrosis factor [KO:K03156]
129329374  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
129329530  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129329994  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
129329995  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
129330010  [KO:K08057]
129330016  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
129330070  SRSF3; serine/arginine-rich splicing factor 3 [KO:K12892]
129330156  SRSF6; serine/arginine-rich splicing factor 6 [KO:K12893]
129330216  CALR3; calreticulin-3 isoform X1 [KO:K08057]
129330526  SRPK1; SRSF protein kinase 1 [KO:K15409] [EC:2.7.11.1]
129330550  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
129330607  BCL2L1; bcl-2-like protein 1 [KO:K04570]
129330873  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
129330943  EIF2B3; translation initiation factor eIF-2B subunit gamma [KO:K03241]
129331257  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
129331288  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
129331346  RNASEL; 2-5A-dependent ribonuclease isoform X1 [KO:K01165]
129331658  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
129331860  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
129332202  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
129332264  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
129332301  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
129332623  EIF2B5; translation initiation factor eIF-2B subunit epsilon [KO:K03240]
129333552  SRSF7; serine/arginine-rich splicing factor 7 isoform X1 [KO:K12896]
129333581  STING1; stimulator of interferon genes protein [KO:K12654]
129333903  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
129334239  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
129334283  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
129334528  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
129334781  RIGI; antiviral innate immune response receptor RIG-I [KO:K12646] [EC:5.6.2.6]
129334950  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
129335154  [KO:K05414]
129335155  [KO:K05414]
129335156  [KO:K05414]
129335157  [KO:K05414]
129335158  [KO:K05414]
129335334  [KO:K04687]
129335339  BID; BH3-interacting domain death agonist [KO:K04726]
129335648  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
129335877  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
129336189  HCFC2; host cell factor 2 [KO:K27390]
129336319  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
129336549  RELA; transcription factor p65 [KO:K04735]
129336555  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
129336994  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
129337092  [KO:K10159]
129337116  TLR2; toll-like receptor 2 [KO:K10159]
129337119  TLR3; toll-like receptor 3 isoform X1 [KO:K05401]
129337174  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
129337229  [KO:K08738]
129337334  IL6; interleukin-6 [KO:K05405]
129337580  RHEB; GTP-binding protein Rheb [KO:K07208]
129337671  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
129337828  EIF2B4; translation initiation factor eIF-2B subunit delta [KO:K03680]
129338317  IRF3; LOW QUALITY PROTEIN: interferon regulatory factor 3 [KO:K05411]
129338668  NXF1; nuclear RNA export factor 1 [KO:K14284]
129338738  ITGB3; integrin beta-3 [KO:K06493]
129339358  CGAS; cyclic GMP-AMP synthase isoform X1 [KO:K17834] [EC:2.7.7.86]
129340065  [KO:K02373]
129340080  TSC2; tuberin isoform X1 [KO:K07207]
129340151  [KO:K04696]
129340172  PILRA; paired immunoglobulin-like type 2 receptor alpha isoform X1 [KO:K15411]
129340239  [KO:K02159]
129340355  [KO:K00922] [EC:2.7.1.153]
129340394  TP53; cellular tumor antigen p53 [KO:K04451]
129340405  BAD; bcl2-associated agonist of cell death [KO:K02158]
129340438  BAX; apoptosis regulator BAX [KO:K02159]
129340727  IRF9; interferon regulatory factor 9 [KO:K04693]
129341049  SRSF9; serine/arginine-rich splicing factor 9 [KO:K21123]
129341211  PTPN11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
129341454  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
129341553  EIF2B1; translation initiation factor eIF-2B subunit alpha [KO:K03239]
129341859  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
129341934  CARD9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
129342000  POU2F3; POU domain, class 2, transcription factor 3 isoform X1 [KO:K09364]
129342005  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
129342021  NECTIN1; nectin-1 [KO:K06081]
129342094  TSC1; hamartin isoform X1 [KO:K07206]
129342159  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
129342322  [KO:K04519]
129342632  C5; complement C5 [KO:K03994]
129342846  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129343292  POU2F2; POU domain, class 2, transcription factor 2 isoform X1 [KO:K09364]
129343342  NECTIN2; nectin-2 isoform X1 [KO:K06531]
129343384  SRSF4; serine/arginine-rich splicing factor 4 [KO:K12893]
129343921  [KO:K28004]
129343981  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
129344458  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
129344501  SRSF1; serine/arginine-rich splicing factor 1 isoform X1 [KO:K12890]
129344828  TNFRSF14; tumor necrosis factor receptor superfamily member 14 [KO:K05152]
129345006  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
129345045  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
129345105  [KO:K07293] [EC:3.1.3.48]
129345363  PDIA3; protein disulfide-isomerase A3 [KO:K08056] [EC:5.3.4.1]
129345368  B2M; beta-2-microglobulin [KO:K08055]
129345462  [KO:K10054] [EC:2.3.2.-]
129345538  [KO:K03158]
129345655  [KO:K10054] [EC:2.3.2.-]
129345981  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
129346015  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
129346016  HCFC1; host cell factor 1 isoform X1 [KO:K14966]
129346041  C3; LOW QUALITY PROTEIN: complement C3 [KO:K03990]
129346112  IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
129346157  CALR; calreticulin [KO:K08057]
129346292  ITGA5; integrin alpha-5 [KO:K06484]
129346528  TNFSF14; tumor necrosis factor ligand superfamily member 14 [KO:K05477]
129346563  CFP; properdin [KO:K15412]
Compound
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C20640  Cyclic GMP-AMP
C20935  2-5A
Reference
PMID:12787566
  Authors
Granger SW, Rickert S
  Title
LIGHT-HVEM signaling and the regulation of T cell-mediated immunity.
  Journal
Cytokine Growth Factor Rev 14:289-96 (2003)
DOI:10.1016/S1359-6101(03)00031-5
Reference
PMID:19495760
  Authors
Steinberg MW, Shui JW, Ware CF, Kronenberg M
  Title
Regulating the mucosal immune system: the contrasting roles of LIGHT, HVEM, and their various partners.
  Journal
Semin Immunopathol 31:207-21 (2009)
DOI:10.1007/s00281-009-0157-4
Reference
PMID:20221426
  Authors
MacLeod IJ, Minson T
  Title
Binding of herpes simplex virus type-1 virions leads to the induction of intracellular signalling in the absence of virus entry.
  Journal
PLoS One 5:e9560 (2010)
DOI:10.1371/journal.pone.0009560
Reference
PMID:23150579
  Authors
Gianni T, Leoni V, Chesnokova LS, Hutt-Fletcher LM, Campadelli-Fiume G
  Title
alphavbeta3-integrin is a major sensor and activator of innate immunity to herpes simplex virus-1.
  Journal
Proc Natl Acad Sci U S A 109:19792-7 (2012)
DOI:10.1073/pnas.1212597109
Reference
PMID:25375272
  Authors
Gianni T, Campadelli-Fiume G
  Title
The epithelial alphavbeta3-integrin boosts the MYD88-dependent TLR2 signaling in response to viral and bacterial components.
  Journal
PLoS Pathog 10:e1004477 (2014)
DOI:10.1371/journal.ppat.1004477
Reference
PMID:15056211
  Authors
Spear PG
  Title
Herpes simplex virus: receptors and ligands for cell entry.
  Journal
Cell Microbiol 6:401-10 (2004)
DOI:10.1111/j.1462-5822.2004.00389.x
Reference
PMID:12855695
  Authors
Boutell C, Everett RD
  Title
The herpes simplex virus type 1 (HSV-1) regulatory protein ICP0 interacts with and Ubiquitinates p53.
  Journal
J Biol Chem 278:36596-602 (2003)
DOI:10.1074/jbc.M300776200
Reference
PMID:24262390
  Authors
Ma Y, He B
  Title
Recognition of herpes simplex viruses: toll-like receptors and beyond.
  Journal
J Mol Biol 426:1133-47 (2014)
DOI:10.1016/j.jmb.2013.11.012
Reference
PMID:26952111
  Authors
Su C, Zhan G, Zheng C
  Title
Evasion of host antiviral innate immunity by HSV-1, an update.
  Journal
Virol J 13:38 (2016)
DOI:10.1186/s12985-016-0495-5
Reference
PMID:21994567
  Authors
Melchjorsen J, Matikainen S, Paludan SR
  Title
Activation and evasion of innate antiviral immunity by herpes simplex virus.
  Journal
Viruses 1:737-59 (2009)
DOI:10.3390/v1030737
Reference
PMID:15276609
  Authors
Morrison LA
  Title
The Toll of herpes simplex virus infection.
  Journal
Trends Microbiol 12:353-6 (2004)
DOI:10.1016/j.tim.2004.06.001
Reference
PMID:29298887
  Authors
Zheng C
  Title
Evasion of Cytosolic DNA-Stimulated Innate Immune Responses by Herpes Simplex Virus 1.
  Journal
J Virol 92:e00099-17 (2018)
DOI:10.1128/JVI.00099-17
Reference
PMID:19344302
  Authors
Grandi P, Peruzzi P, Reinhart B, Cohen JB, Chiocca EA, Glorioso JC
  Title
Design and application of oncolytic HSV vectors for glioblastoma therapy.
  Journal
Expert Rev Neurother 9:505-17 (2009)
DOI:10.1586/ern.09.9
Reference
PMID:23115300
  Authors
Lussignol M, Queval C, Bernet-Camard MF, Cotte-Laffitte J, Beau I, Codogno P, Esclatine A
  Title
The herpes simplex virus 1 Us11 protein inhibits autophagy through its interaction with the protein kinase PKR.
  Journal
J Virol 87:859-71 (2013)
DOI:10.1128/JVI.01158-12
Reference
PMID:17229694
  Authors
Sanchez R, Mohr I
  Title
Inhibition of cellular 2'-5' oligoadenylate synthetase by the herpes simplex virus type 1 Us11 protein.
  Journal
J Virol 81:3455-64 (2007)
DOI:10.1128/JVI.02520-06
Reference
PMID:12826401
  Authors
Wysocka J, Herr W
  Title
The herpes simplex virus VP16-induced complex: the makings of a regulatory switch.
  Journal
Trends Biochem Sci 28:294-304 (2003)
DOI:10.1016/S0968-0004(03)00088-4
Reference
PMID:27367734
  Authors
Fleming SB
  Title
Viral Inhibition of the IFN-Induced JAK/STAT Signalling Pathway: Development of Live Attenuated Vaccines by Mutation of Viral-Encoded IFN-Antagonists.
  Journal
Vaccines (Basel) 4:23 (2016)
DOI:10.3390/vaccines4030023
Reference
PMID:15163721
  Authors
Yokota S, Yokosawa N, Okabayashi T, Suzutani T, Miura S, Jimbow K, Fujii N
  Title
Induction of suppressor of cytokine signaling-3 by herpes simplex virus type 1 contributes to inhibition of the interferon signaling pathway.
  Journal
J Virol 78:6282-6 (2004)
DOI:10.1128/JVI.78.12.6282-6286.2004
Reference
PMID:23864622
  Authors
Gu H, Zheng Y, Roizman B
  Title
Interaction of herpes simplex virus ICP0 with ND10 bodies: a sequential process of adhesion, fusion, and retention.
  Journal
J Virol 87:10244-54 (2013)
DOI:10.1128/JVI.01487-13
Reference
PMID:21994592
  Authors
Tavalai N, Stamminger T
  Title
Interplay between Herpesvirus Infection and Host Defense by PML Nuclear Bodies.
  Journal
Viruses 1:1240-64 (2009)
DOI:10.3390/v1031240
Reference
PMID:21146386
  Authors
Horst D, Verweij MC, Davison AJ, Ressing ME, Wiertz EJ
  Title
Viral evasion of T cell immunity: ancient mechanisms offering new applications.
  Journal
Curr Opin Immunol 23:96-103 (2011)
DOI:10.1016/j.coi.2010.11.005
Reference
PMID:12960333
  Authors
Neumann J, Eis-Hubinger AM, Koch N
  Title
Herpes simplex virus type 1 targets the MHC class II processing pathway for immune evasion.
  Journal
J Immunol 171:3075-83 (2003)
DOI:10.4049/jimmunol.171.6.3075
Reference
PMID:25798530
  Authors
Liu X, Cohen JI
  Title
The role of PI3K/Akt in human herpesvirus infection: From the bench to the bedside.
  Journal
Virology 479-480:568-77 (2015)
DOI:10.1016/j.virol.2015.02.040
Reference
PMID:28468873
  Authors
Vink EI, Smiley JR, Mohr I
  Title
Subversion of Host Responses to Energy Insufficiency by Us3 Supports Herpes Simplex Virus 1 Replication during Stress.
  Journal
J Virol 91:e00295-17 (2017)
DOI:10.1128/JVI.00295-17
Reference
PMID:18508584
  Authors
Sandri-Goldin RM
  Title
The many roles of the regulatory protein ICP27 during herpes simplex virus infection.
  Journal
Front Biosci 13:5241-56 (2008)
DOI:10.2741/3078
Reference
PMID:15078920
  Authors
Sandri-Goldin RM
  Title
Viral regulation of mRNA export.
  Journal
J Virol 78:4389-96 (2004)
DOI:10.1128/JVI.78.9.4389-4396.2004
Reference
PMID:27154074
  Authors
Yu X, He S
  Title
The interplay between human herpes simplex virus infection and the apoptosis and necroptosis cell death pathways.
  Journal
Virol J 13:77 (2016)
DOI:10.1186/s12985-016-0528-0
Related
pathway
emc03040  Spliceosome
emc03050  Proteasome
emc04115  p53 signaling pathway
emc04210  Apoptosis
emc04620  Toll-like receptor signaling pathway
emc04622  RIG-I-like receptor signaling pathway
KO pathway
ko05168   

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