KEGG   PATHWAY: oor05168
Entry
oor05168                    Pathway                                
Name
Herpes simplex virus 1 infection - Orcinus orca (killer whale)
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
oor05168  Herpes simplex virus 1 infection
oor05168

Disease
H00365  Herpes simplex virus infection
Organism
Orcinus orca (killer whale) [GN:oor]
Gene
101269870  TNF; tumor necrosis factor [KO:K03156]
101270123  LTA; lymphotoxin-alpha [KO:K05468]
101270256  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase isoform X1 [KO:K16195] [EC:2.7.11.1]
101270273  SRPK1; LOW QUALITY PROTEIN: SRSF protein kinase 1 [KO:K15409] [EC:2.7.11.1]
101270312  EIF2B5; translation initiation factor eIF-2B subunit epsilon [KO:K03240]
101270342  RELA; transcription factor p65 isoform X1 [KO:K04735]
101270820  [KO:K12893]
101270874  SRSF1; serine/arginine-rich splicing factor 1 [KO:K12890]
101270971  CD74; HLA class II histocompatibility antigen gamma chain isoform X1 [KO:K06505]
101271022  NECTIN2; nectin-2 isoform X2 [KO:K06531]
101271323  IFIH1; interferon-induced helicase C domain-containing protein 1 isoform X2 [KO:K12647] [EC:5.6.2.6]
101271374  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
101271677  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
101271709  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
101271749  [KO:K06751]
101272095  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101272168  IRF3; interferon regulatory factor 3 [KO:K05411]
101272428  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
101272436  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
101272458  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
101272505  EIF2AK1; eukaryotic translation initiation factor 2-alpha kinase 1 isoform X3 [KO:K16194] [EC:2.7.11.1]
101272815  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
101272835  IL12B; interleukin-12 subunit beta [KO:K05425]
101272869  [KO:K08738]
101272896  CFP; properdin [KO:K15412]
101272962  FADD; FAS-associated death domain protein isoform X1 [KO:K02373]
101273316  AKT1; RAC-alpha serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101273610  EIF2B4; translation initiation factor eIF-2B subunit delta isoform X2 [KO:K03680]
101273673  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X4 [KO:K07211] [EC:2.7.11.10]
101273776  [KO:K12499]
101274041  [KO:K05414]
101274967  BAD; bcl2-associated agonist of cell death [KO:K02158]
101275016  [KO:K05414]
101275089  SRC; proto-oncogene tyrosine-protein kinase Src isoform X3 [KO:K05704] [EC:2.7.10.2]
101275177  [KO:K08055]
101275188  ITGB3; integrin beta-3 [KO:K06493]
101275275  [KO:K05414]
101275353  ITGA5; integrin alpha-5 [KO:K06484]
101275383  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
101275531  ALYREF; THO complex subunit 4 [KO:K12881]
101275631  [KO:K08738]
101275677  TSC1; hamartin isoform X1 [KO:K07206]
101275872  STING1; stimulator of interferon genes protein isoform X1 [KO:K12654]
101275987  [KO:K06752]
101276053  TLR2; toll-like receptor 2 [KO:K10159]
101276054  IFNGR1; interferon gamma receptor 1 [KO:K05132]
101276336  TSC2; tuberin isoform X9 [KO:K07207]
101276381  SP100; nuclear autoantigen Sp-100 isoform X1 [KO:K15413]
101276394  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
101276578  [KO:K06751]
101276649  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
101276750  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
101276823  [KO:K06752]
101277081  [KO:K06752]
101277165  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
101277446  RIGI; LOW QUALITY PROTEIN: antiviral innate immune response receptor RIG-I [KO:K12646] [EC:5.6.2.6]
101277458  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
101277553  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
101277568  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101277745  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
101277868  OAS2; LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 2 [KO:K14216] [EC:2.7.7.84]
101278075  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101278346  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X2 [KO:K11219] [EC:2.7.10.2]
101278425  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
101278583  TLR3; toll-like receptor 3 [KO:K05401]
101278678  B2M; beta-2-microglobulin [KO:K08055]
101278974  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
101279088  IL12A; interleukin-12 subunit alpha [KO:K05406]
101279236  [KO:K03680]
101279383  C5; complement C5 isoform X1 [KO:K03994]
101279441  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
101279584  CALR; calreticulin [KO:K08057]
101279857  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101280074  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
101280171  POU2F3; POU domain, class 2, transcription factor 3 isoform X1 [KO:K09364]
101280303  APAF1; apoptotic protease-activating factor 1 isoform X4 [KO:K02084]
101280558  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
101280569  POU2F1; POU domain, class 2, transcription factor 1 isoform X1 [KO:K09364]
101280639  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X2 [KO:K04730] [EC:2.7.11.1]
101280766  TNFSF14; tumor necrosis factor ligand superfamily member 14 isoform X1 [KO:K05477]
101280970  EIF2B3; translation initiation factor eIF-2B subunit gamma [KO:K03241]
101281072  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
101281288  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
101281303  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
101281331  POU2F2; POU domain, class 2, transcription factor 2 isoform X9 [KO:K09364]
101281352  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X2 [KO:K02649]
101281360  SRSF9; serine/arginine-rich splicing factor 9 [KO:K21123]
101281391  SRSF4; serine/arginine-rich splicing factor 4 isoform X1 [KO:K12893]
101281395  BAK1; bcl-2 homologous antagonist/killer isoform X2 [KO:K14021]
101281425  C3; complement C3 [KO:K03990]
101281591  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
101281675  SRSF2; serine/arginine-rich splicing factor 2 [KO:K12891]
101281780  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
101281783  IL6; LOW QUALITY PROTEIN: interleukin-6 [KO:K05405]
101281966  [KO:K15411]
101281971  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
101282451  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
101282458  HCFC1; host cell factor 1 isoform X7 [KO:K14966]
101282502  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
101282672  BST2; bone marrow stromal antigen 2 [KO:K06731]
101282675  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X2 [KO:K04403]
101282830  PDIA3; protein disulfide-isomerase A3 isoform X1 [KO:K08056] [EC:5.3.4.1]
101282933  IFNG; interferon gamma [KO:K04687]
101283011  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101283052  [KO:K08738]
101283089  SRSF6; serine/arginine-rich splicing factor 6 isoform X1 [KO:K12893]
101283102  PML; protein PML isoform X2 [KO:K10054] [EC:2.3.2.-]
101283238  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
101283649  DAXX; death domain-associated protein 6 isoform X1 [KO:K02308]
101283958  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
101283961  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101284022  FAS; tumor necrosis factor receptor superfamily member 6 isoform X5 [KO:K04390]
101284211  NXF1; nuclear RNA export factor 1 isoform X4 [KO:K14284]
101284215  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
101284249  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
101284313  TAPBP; tapasin isoform X2 [KO:K08058]
101284365  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
101284556  MAVS; mitochondrial antiviral-signaling protein isoform X4 [KO:K12648]
101284636  CARD9; caspase recruitment domain-containing protein 9 isoform X2 [KO:K12794]
101284780  EIF2B2; translation initiation factor eIF-2B subunit beta [KO:K03754]
101284843  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
101284892  IL1B; interleukin-1 beta isoform X2 [KO:K04519]
101285243  [KO:K12892]
101285349  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
101285437  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101285623  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
101285670  TP53; cellular tumor antigen p53 isoform X2 [KO:K04451]
101285763  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
101286095  [KO:K14284]
101286130  RNASEL; 2-5A-dependent ribonuclease isoform X2 [KO:K01165]
101286490  RHEB; GTP-binding protein Rheb isoform X1 [KO:K07208]
101286983  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
101287280  [KO:K14284]
101287367  [KO:K05414]
101287516  [KO:K14284]
101287624  [KO:K06752]
101287781  SRSF7; serine/arginine-rich splicing factor 7 isoform X1 [KO:K12896]
101287882  [KO:K06752]
101287933  SRSF5; serine/arginine-rich splicing factor 5 isoform X1 [KO:K12893]
101288063  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
101288103  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101288182  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X5 [KO:K07293] [EC:3.1.3.48]
101288184  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
101288385  [KO:K06752]
101288810  SRSF3; serine/arginine-rich splicing factor 3 [KO:K12892]
101288996  EIF2AK4; eIF-2-alpha kinase GCN2 isoform X1 [KO:K16196] [EC:2.7.11.1]
101289058  IFNB1; interferon beta [KO:K05415]
101289068  HCFC2; host cell factor 2 isoform X3 [KO:K27390]
101289082  NECTIN1; nectin-1 isoform X1 [KO:K06081]
101289148  [KO:K10161]
101289192  [KO:K14216] [EC:2.7.7.84]
101289225  [KO:K06752]
101289477  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101289557  CGAS; cyclic GMP-AMP synthase isoform X1 [KO:K17834] [EC:2.7.7.86]
101289644  ZC3HAV1; zinc finger CCCH-type antiviral protein 1 isoform X1 [KO:K28004]
101289706  [KO:K14624]
101289708  TAP1; antigen peptide transporter 1 [KO:K05653] [EC:7.4.2.14]
101289826  EIF2B1; translation initiation factor eIF-2B subunit alpha [KO:K03239]
101289847  CASP3; caspase-3 isoform X2 [KO:K02187] [EC:3.4.22.56]
101290315  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
101290371  TAP2; antigen peptide transporter 2 [KO:K05654] [EC:7.4.2.14]
105747703  [KO:K08738]
105747906  [KO:K08738]
105748394  [KO:K06751]
117203203  [KO:K08738]
125963661  [KO:K08055]
125964698  [KO:K05414]
125964699  [KO:K05414]
125964701  [KO:K05414]
125964702  [KO:K05414]
125964703  [KO:K05414]
125965560  [KO:K06751]
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:E23 (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
oor03040  Spliceosome
oor03050  Proteasome
oor04115  p53 signaling pathway
oor04151  PI3K-Akt signaling pathway
oor04210  Apoptosis
oor04610  Complement and coagulation cascades
oor04612  Antigen processing and presentation
oor04620  Toll-like receptor signaling pathway
oor04622  RIG-I-like receptor signaling pathway
oor04630  JAK-STAT signaling pathway
KO pathway
ko05168   

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