KEGG   PATHWAY: ko05168
Entry
ko05168                     Pathway                                
Name
Herpes simplex virus 1 infection
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
ko05168  Herpes simplex virus 1 infection
ko05168

Disease
H00365  Herpes simplex virus infection
Orthology
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01165  RNASEL; ribonuclease L
K02084  APAF1; apoptotic protease-activating factor
K02158  BAD; Bcl-2-antagonist of cell death
K02159  BAX; apoptosis regulator BAX
K02161  BCL2; apoptosis regulator Bcl-2
K02187  CASP3; caspase 3 [EC:3.4.22.56]
K02308  DAXX; death-associated protein 6
K02373  FADD; FAS-associated death domain protein
K02580  NFKB1; nuclear factor NF-kappa-B p105 subunit
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K03156  TNF, TNFA; tumor necrosis factor superfamily, member 2
K03158  TNFRSF1A, TNFR1, CD120a; tumor necrosis factor receptor superfamily member 1A
K03171  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein
K03173  TRAF2; TNF receptor-associated factor 2 [EC:2.3.2.27]
K03174  TRAF3; TNF receptor-associated factor 3
K03175  TRAF6; TNF receptor-associated factor 6 [EC:2.3.2.27]
K03237  EIF2S1; translation initiation factor 2 subunit 1
K03239  EIF2B1; translation initiation factor eIF-2B subunit alpha
K03240  EIF2B5; translation initiation factor eIF-2B subunit epsilon
K03241  EIF2B3; translation initiation factor eIF-2B subunit gamma
K03680  EIF2B4; translation initiation factor eIF-2B subunit delta
K03754  EIF2B2; translation initiation factor eIF-2B subunit beta
K03990  C3; complement component 3
K03994  C5; complement component 5
K04389  TNFSF6, FASL, CD178; tumor necrosis factor ligand superfamily member 6
K04390  TNFRSF6, FAS, CD95; tumor necrosis factor receptor superfamily member 6
K04398  CASP8; caspase 8 [EC:3.4.22.61]
K04399  CASP9; caspase 9 [EC:3.4.22.62]
K04403  MAP3K7IP1, TAB1; TAK1-binding protein 1
K04404  MAP3K7IP2, TAB2; TAK1-binding protein 2
K04427  MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25]
K04447  JAK2; Janus kinase 2 [EC:2.7.10.2]
K04451  TP53, P53; tumor protein p53
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04467  IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K04519  IL1B; interleukin 1 beta
K04570  BCL2L1, bcl-xL; Bcl-2-like 1 (apoptosis regulator Bcl-X)
K04687  IFNG; interferon gamma
K04693  IRF9, ISGF3G, P48; interferon regulatory factor 9
K04696  SOCS3, CIS3; suppressor of cytokine signaling 3
K04726  BID; BH3 interacting domain death agonist
K04729  MYD88; myeloid differentiation primary response protein MyD88
K04730  IRAK1; interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1]
K04733  IRAK4; interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1]
K04734  NFKBIA; NF-kappa-B inhibitor alpha
K04735  RELA; transcription factor p65
K05130  IFNAR1; interferon receptor 1
K05131  IFNAR2; interferon receptor 2
K05132  IFNGR1, CD119; interferon gamma receptor 1
K05133  IFNGR2; interferon gamma receptor 2
K05152  TNFRSF14, HVEM, CD270; tumor necrosis factor receptor superfamily member 14
K05401  TLR3, CD283; toll-like receptor 3
K05405  IL6; interleukin 6
K05406  IL12A; interleukin 12A
K05410  TBK1; TANK-binding kinase 1 [EC:2.7.11.10]
K05411  IRF3; interferon regulatory factor 3
K05414  IFNA; interferon alpha
K05415  IFNB; interferon beta
K05425  IL12B; interleukin 12B
K05468  LTA, TNFB; lymphotoxin alpha (TNF superfamily, member 1)
K05477  TNFSF14, LIGHT, CD258; tumor necrosis factor ligand superfamily member 14
K05653  ABCB2, TAP1; ATP-binding cassette, subfamily B (MDR/TAP), member 2 [EC:7.4.2.14]
K05654  ABCB3, TAP2; ATP-binding cassette, subfamily B (MDR/TAP), member 3 [EC:7.4.2.14]
K05704  SRC; tyrosine-protein kinase Src [EC:2.7.10.2]
K05842  TRIF; toll-like receptor adapter molecule 1
K05855  SYK; spleen tyrosine kinase [EC:2.7.10.2]
K06081  NECTIN1, PVRL1, CD111; poliovirus receptor-related protein 1
K06269  PPP1C; serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16]
K06484  ITGA5, CD49e; integrin alpha 5
K06493  ITGB3, CD61; integrin beta 3
K06505  CD74, DHLAG; CD74 antigen
K06531  NECTIN2, PVRL2, CD112; poliovirus receptor-related protein 2
K06731  BST2, CD317; bone marrow stromal cell antigen 2
K06751  MHC1; MHC class I antigen
K06752  MHC2; MHC class II antigen
K07203  MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1]
K07205  EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1
K07206  TSC1; tuberous sclerosis 1
K07207  TSC2; tuberous sclerosis 2
K07208  RHEB; Ras homolog enriched in brain
K07209  IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K07210  IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma
K07211  IKBKE, IKKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [EC:2.7.11.10]
K07293  PTPN11, SHP2; tyrosine-protein phosphatase non-receptor type 11 [EC:3.1.3.48]
K08055  B2M; beta-2-microglobulin
K08056  PDIA3, GRP58; protein disulfide-isomerase A3 [EC:5.3.4.1]
K08057  CALR; calreticulin
K08058  TAPBP; TAP binding protein (tapasin)
K08738  CYC; cytochrome c
K08860  EIF2AK3, PERK; eukaryotic translation initiation factor 2-alpha kinase 3 [EC:2.7.11.1]
K09364  POU2F, OTF; POU domain transcription factor, class 2
K09447  IRF7; interferon regulatory factor 7
K09849  TRAF5; TNF receptor-associated factor 5
K10054  PML, TRIM19; E3 SUMO-protein ligase PML [EC:2.3.2.-]
K10159  TLR2, CD282; toll-like receptor 2
K10161  TLR9, CD289; toll-like receptor 9
K11217  JAK1; Janus kinase 1 [EC:2.7.10.2]
K11219  TYK2; non-receptor tyrosine-protein kinase TYK2 [EC:2.7.10.2]
K11220  STAT1; signal transducer and activator of transcription 1
K11221  STAT2; signal transducer and activator of transcription 2
K12499  CCL5; C-C motif chemokine 5
K12646  RIGI, DDX58; ATP-dependent RNA helicase DDX58 [EC:5.6.2.6]
K12647  IFIH1, MDA5; interferon-induced helicase C domain-containing protein 1 [EC:5.6.2.6]
K12648  MAVS, IPS1; mitochondrial antiviral-signaling protein
K12654  STING1, TMEM173, MITA; stimulator of interferon genes protein
K12794  CARD9; caspase recruitment domain-containing protein 9
K12881  THOC4, ALY; THO complex subunit 4
K12890  SRSF1, SFRS1, ASF, SF2; serine/arginine-rich splicing factor 1
K12891  SRSF2_8, SFRS2A_B; serine/arginine-rich splicing factor 2/8
K12892  SRSF3, SFRS3; serine/arginine-rich splicing factor 3
K12893  SRSF4_5_6, SFRS4_5_6; serine/arginine-rich splicing factor 4/5/6
K12896  SRSF7, SFRS7; serine/arginine-rich splicing factor 7
K14021  BAK, BAK1; Bcl-2 homologous antagonist/killer
K14216  OAS; 2'-5'-oligoadenylate synthetase [EC:2.7.7.84]
K14284  NXF, TAP, MEX67; nuclear RNA export factor
K14624  CCL2, MCP1; C-C motif chemokine 2
K14966  HCFC1; host cell factor 1
K15409  SRPK1; serine/threonine-protein kinase SRPK1 [EC:2.7.11.1]
K15411  PILR; paired immunoglobulin-like type 2 receptor
K15412  CFP; complement factor properdin
K15413  SP100; nuclear body protein Sp100
K16060  BIRC2_3; baculoviral IAP repeat-containing protein 2/3
K16194  EIF2AK1; eukaryotic translation initiation factor 2-alpha kinase 1 [EC:2.7.11.1]
K16195  EIF2AK2; eukaryotic translation initiation factor 2-alpha kinase 2 [EC:2.7.11.1]
K16196  EIF2AK4; eukaryotic translation initiation factor 2-alpha kinase 4 [EC:2.7.11.1]
K17834  CGAS, MB21D1; cyclic GMP-AMP synthase [EC:2.7.7.86]
K19255  gB; Herpesviridae envelope glycoprotein B
K19256  gC; Simplexvirus envelope glycoprotein C
K19264  gD; Simplexvirus envelope glycoprotein D
K19434  gH, UL22; Simplexvirus envelope glycoprotein H
K19435  gL, UL1; Simplexvirus envelope glycoprotein L
K19436  ICP0, RL2; Simplexvirus E3 ubiquitin-protein ligase ICP0
K19437  RL1; Simplexvirus neurovirulence factor ICP34.5
K19438  US11; Simplexvirus RNA-binding protein
K19439  US3; Simplexvirus serine/threonine-protein kinase US3 [EC:2.7.11.1]
K19440  UL13; Simplexvirus serine/threonine-protein kinase UL13 [EC:2.7.11.1]
K19441  US1; Simplexvirus transcriptional regulator ICP22
K19443  UL54; Simplexvirus mRNA export factor
K19444  UL48; Simplexvirus tegument protein VP16
K19445  ICP4, RS1; Simplexvirus major viral transcription factor ICP4
K19446  US12; Simplexvirus ICP47 protein
K19447  UL41; Simplexvirus virion host shutoff protein [EC:3.1.27.-]
K19448  UL39; Simplexvirus ribonucleoside-diphosphate reductase large subunit [EC:1.17.4.1]
K21075  UL36, UL48; Herpesviridae large tegument protein deneddylase [EC:3.4.19.12 3.4.22.-]
K21123  SRSF9, SFRS9; serine/arginine-rich splicing factor 9
K23212  UL46; Simplexvirus tegument protein VP11/12
K27390  HCFC2; host cell factor 2
K28004  ZC3HAV1; zinc finger CCCH-type antiviral protein 1
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
ko03040  Spliceosome
ko03050  Proteasome
ko04115  p53 signaling pathway
ko04151  PI3K-Akt signaling pathway
ko04210  Apoptosis
ko04610  Complement and coagulation cascades
ko04612  Antigen processing and presentation
ko04620  Toll-like receptor signaling pathway
ko04622  RIG-I-like receptor signaling pathway
ko04630  JAK-STAT signaling pathway

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