KEGG   PATHWAY: hsa05162
Entry
hsa05162                    Pathway                                
Name
Measles - Homo sapiens (human)
Description
Measles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. MV infection is characterized by virus-induced immune suppression that can lead to increased susceptibility to secondary bacterial and viral infections. The P, V and C proteins act as virulence factors to suppress innate immune response in host by inhibiting signaling for both type I IFN induction and JAK/STAT-mediated interferon-stimulated gene (ISG) induction. Moreover,  H protein expressed on viral particles and binding to SLAM or CD46,  as well as N protein liberated from infected cells and interacting with Fc-gamma R, causes an inhibition of IL-12 synthesis in dendritic cells. IL-12 is a key cytokine inducing cellular immune responses to protect host from the harm caused by pathogenic infections.
Class
Human Diseases; Infectious disease: viral
Pathway map
hsa05162  Measles
hsa05162

Network
  Element
N00684  MV F/H to CD28-PI3K signaling pathway
N00685  MV V to RIG-I-IRF7/3 signaling pathway
N00686  MV N to RIG-I-IRF7/3 signaling pathway
N00687  MV V/C to RIG-I-IRF7/3 signaling pathway
N00689  MV V/P/C to RIG-I-NFKB signaling pathway
N00691  MV V to TLR7/9-IRF7 signaling pathway
N00692  MV P to TLR2/4-NFKB signaling pathway
N00693  MV V/P to IFN signaling pathway
N00694  MV V/P/C to IFN signaling pathway
N00695  MV V to p73-mediated transcription
N00696  MV C to PKR-eIF2alpha signaling pathway
N00697  HV P to p53-mediated transcription
Disease
H00394  Measles
Drug
D03305  Interferon alfa (NAMALWA) (JP18)
Organism
Homo sapiens (human) [GN:hsa]
Gene
4179  CD46; CD46 molecule [KO:K04007]
4478  MSN; moesin [KO:K05763]
6504  SLAMF1; signaling lymphocytic activation molecule family member 1 [KO:K06536]
10332  CLEC4M; C-type lectin domain family 4 member M [KO:K06563]
30835  CD209; CD209 molecule [KO:K06563]
23586  RIGI; RNA sensor RIG-I [KO:K12646] [EC:5.6.2.6]
64135  IFIH1; interferon induced with helicase C domain 1 [KO:K12647] [EC:5.6.2.6]
57506  MAVS; mitochondrial antiviral signaling protein [KO:K12648]
7187  TRAF3; TNF receptor associated factor 3 [KO:K03174]
9641  IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
29110  TBK1; TANK binding kinase 1 [KO:K05410] [EC:2.7.11.10]
3661  IRF3; interferon regulatory factor 3 [KO:K05411]
1147  CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:2.7.11.10]
3551  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
8517  IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210]
4793  NFKBIB; NFKB inhibitor beta [KO:K02581]
4792  NFKBIA; NFKB inhibitor alpha [KO:K04734]
4790  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
5970  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
51284  TLR7; toll like receptor 7 [KO:K05404]
54106  TLR9; toll like receptor 9 [KO:K10161]
4615  MYD88; MYD88 innate immune signal transduction adaptor [KO:K04729]
3654  IRAK1; interleukin 1 receptor associated kinase 1 [KO:K04730] [EC:2.7.11.1]
51135  IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:2.7.11.1]
3665  IRF7; interferon regulatory factor 7 [KO:K09447]
3439  IFNA1; interferon alpha 1 [KO:K05414]
3440  IFNA2; interferon alpha 2 [KO:K05414]
3441  IFNA4; interferon alpha 4 [KO:K05414]
3442  IFNA5; interferon alpha 5 [KO:K05414]
3443  IFNA6; interferon alpha 6 [KO:K05414]
3444  IFNA7; interferon alpha 7 [KO:K05414]
3445  IFNA8; interferon alpha 8 [KO:K05414]
3446  IFNA10; interferon alpha 10 [KO:K05414]
3447  IFNA13; interferon alpha 13 [KO:K05414]
3448  IFNA14; interferon alpha 14 [KO:K05414]
3449  IFNA16; interferon alpha 16 [KO:K05414]
3451  IFNA17; interferon alpha 17 [KO:K05414]
3452  IFNA21; interferon alpha 21 [KO:K05414]
3456  IFNB1; interferon beta 1 [KO:K05415]
7097  TLR2; toll like receptor 2 [KO:K10159]
7099  TLR4; toll like receptor 4 [KO:K10160]
7189  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
1457  CSNK2A1; casein kinase 2 alpha 1 [KO:K03097] [EC:2.7.11.1]
1459  CSNK2A2; casein kinase 2 alpha 2 [KO:K03097] [EC:2.7.11.1]
283106  CSNK2A3; casein kinase 2 alpha 3 [KO:K03097] [EC:2.7.11.1]
1460  CSNK2B; casein kinase 2 beta [KO:K03115]
7128  TNFAIP3; TNF alpha induced protein 3 [KO:K11859] [EC:3.4.19.12]
6885  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
23118  TAB2; TGF-beta activated kinase 1 (MAP3K7) binding protein 2 [KO:K04404]
5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
3725  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
2353  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
3552  IL1A; interleukin 1 alpha [KO:K04383]
3553  IL1B; interleukin 1 beta [KO:K04519]
3569  IL6; interleukin 6 [KO:K05405]
3592  IL12A; interleukin 12A [KO:K05406]
3593  IL12B; interleukin 12B [KO:K05425]
3454  IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130]
3455  IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131]
10399  RACK1; receptor for activated C kinase 1 [KO:K14753]
3716  JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
7297  TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
6772  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
6773  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
10379  IRF9; interferon regulatory factor 9 [KO:K04693]
4938  OAS1; 2'-5'-oligoadenylate synthetase 1 [KO:K14216] [EC:2.7.7.84]
4939  OAS2; 2'-5'-oligoadenylate synthetase 2 [KO:K14216] [EC:2.7.7.84]
4940  OAS3; 2'-5'-oligoadenylate synthetase 3 [KO:K14216] [EC:2.7.7.84]
103  ADAR; adenosine deaminase RNA specific [KO:K12968] [EC:3.5.4.37]
4599  MX1; MX dynamin like GTPase 1 [KO:K14754]
4600  MX2; MX dynamin like GTPase 2 [KO:K14754]
27102  EIF2AK1; eukaryotic translation initiation factor 2 alpha kinase 1 [KO:K16194] [EC:2.7.11.1]
5610  EIF2AK2; eukaryotic translation initiation factor 2 alpha kinase 2 [KO:K16195] [EC:2.7.11.1]
9451  EIF2AK3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
440275  EIF2AK4; eukaryotic translation initiation factor 2 alpha kinase 4 [KO:K16196] [EC:2.7.11.1]
9367  RAB9A; RAB9A, member RAS oncogene family [KO:K07899]
51209  RAB9B; RAB9B, member RAS oncogene family [KO:K07900]
3312  HSPA8; heat shock protein family A (Hsp70) member 8 [KO:K03283]
3303  HSPA1A; heat shock protein family A (Hsp70) member 1A [KO:K03283]
3305  HSPA1L; heat shock protein family A (Hsp70) member 1 like [KO:K03283]
3304  HSPA1B; heat shock protein family A (Hsp70) member 1B [KO:K03283]
3310  HSPA6; heat shock protein family A (Hsp70) member 6 [KO:K03283]
8667  EIF3H; eukaryotic translation initiation factor 3 subunit H [KO:K03247]
1965  EIF2S1; eukaryotic translation initiation factor 2 subunit alpha [KO:K03237]
25898  RCHY1; ring finger and CHY zinc finger domain containing 1 [KO:K10144] [EC:2.3.2.27]
7157  TP53; tumor protein p53 [KO:K04451]
7161  TP73; tumor protein p73 [KO:K10148]
27113  BBC3; BCL2 binding component 3 [KO:K10132]
356  FASLG; Fas ligand [KO:K04389]
355  FAS; Fas cell surface death receptor [KO:K04390]
8717  TRADD; TNFRSF1A associated via death domain [KO:K03171]
8772  FADD; Fas associated via death domain [KO:K02373]
841  CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
637  BID; BH3 interacting domain death agonist [KO:K04726]
581  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
578  BAK1; BCL2 antagonist/killer 1 [KO:K14021]
596  BCL2; BCL2 apoptosis regulator [KO:K02161]
598  BCL2L1; BCL2 like 1 [KO:K04570]
572  BAD; BCL2 associated agonist of cell death [KO:K02158]
54205  CYCS; cytochrome c, somatic [KO:K08738]
317  APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
842  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
836  CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
1027  CDKN1B; cyclin dependent kinase inhibitor 1B [KO:K06624]
595  CCND1; cyclin D1 [KO:K04503]
894  CCND2; cyclin D2 [KO:K10151]
896  CCND3; cyclin D3 [KO:K10152]
898  CCNE1; cyclin E1 [KO:K06626]
9134  CCNE2; cyclin E2 [KO:K06626]
1019  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
1021  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
1017  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
915  CD3D; CD3 delta subunit of T-cell receptor complex [KO:K06450]
916  CD3E; CD3 epsilon subunit of T-cell receptor complex [KO:K06451]
917  CD3G; CD3 gamma subunit of T-cell receptor complex [KO:K06452]
940  CD28; CD28 molecule [KO:K06470]
3558  IL2; interleukin 2 [KO:K05429]
3559  IL2RA; interleukin 2 receptor subunit alpha [KO:K05068]
3560  IL2RB; interleukin 2 receptor subunit beta [KO:K05069]
3561  IL2RG; interleukin 2 receptor subunit gamma [KO:K05070]
5295  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
5296  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
5290  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
868  CBLB; Cbl proto-oncogene B [KO:K22517] [EC:2.3.2.27]
207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
2932  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
3718  JAK3; Janus kinase 3 [KO:K11218] [EC:2.7.10.2]
6774  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
6776  STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
6777  STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
2213  FCGR2B; Fc gamma receptor IIb [KO:K12560]
Compound
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:19203113
  Authors
Schneider-Schaulies S, Schneider-Schaulies J
  Title
Measles virus-induced immunosuppression.
  Journal
Curr Top Microbiol Immunol 330:243-69 (2009)
DOI:10.1007/978-3-540-70617-5_12
Reference
PMID:19203114
  Authors
Hahm B
  Title
Hostile communication of measles virus with host innate immunity and dendritic cells.
  Journal
Curr Top Microbiol Immunol 330:271-87 (2009)
DOI:10.1007/978-3-540-70617-5_13
Reference
PMID:19198566
  Authors
Gerlier D, Valentin H
  Title
Measles virus interaction with host cells and impact on innate immunity.
  Journal
Curr Top Microbiol Immunol 329:163-91 (2009)
DOI:10.1007/978-3-540-70523-9_8
Reference
PMID:16690907
  Authors
Schneider-Schaulies S, Dittmer U
  Title
Silencing T cells or T-cell silencing: concepts in virus-induced immunosuppression.
  Journal
J Gen Virol 87:1423-38 (2006)
DOI:10.1099/vir.0.81713-0
Reference
PMID:22049305
  Authors
Avota E, Gassert E, Schneider-Schaulies S
  Title
Cytoskeletal dynamics: concepts in measles virus replication and immunomodulation.
  Journal
Viruses 3:102-17 (2011)
DOI:10.3390/v3020102
Reference
PMID:27854326
  Authors
Jiang Y, Qin Y, Chen M
  Title
Host-Pathogen Interactions in Measles Virus Replication and Anti-Viral Immunity.
  Journal
Viruses 8:E308 (2016)
DOI:10.3390/v8110308
Reference
PMID:18922877
  Authors
Pfaller CK, Conzelmann KK
  Title
Measles virus V protein is a decoy substrate for IkappaB kinase alpha and prevents Toll-like receptor 7/9-mediated interferon induction.
  Journal
J Virol 82:12365-73 (2008)
DOI:10.1128/JVI.01321-08
Reference
PMID:17720800
  Authors
Yokota S, Okabayashi T, Yokosawa N, Fujii N
  Title
Measles virus P protein suppresses Toll-like receptor signal through up-regulation of ubiquitin-modifying enzyme A20.
  Journal
FASEB J 22:74-83 (2008)
DOI:10.1096/fj.07-8976com
Reference
PMID:23146309
  Authors
Delpeut S, Noyce RS, Siu RW, Richardson CD
  Title
Host factors and measles virus replication.
  Journal
Curr Opin Virol 2:773-83 (2012)
DOI:10.1016/j.coviro.2012.10.008
Reference
PMID:26878224
  Authors
Shah M, Anwar MA, Kim JH, Choi S
  Title
Advances in Antiviral Therapies Targeting Toll-like Receptors.
  Journal
Expert Opin Investig Drugs 25:437-53 (2016)
DOI:10.1517/13543784.2016.1154040
Reference
PMID:12620806
  Authors
Yokota S, Saito H, Kubota T, Yokosawa N, Amano K, Fujii N
  Title
Measles virus suppresses interferon-alpha signaling pathway: suppression of Jak1 phosphorylation and association of viral accessory proteins, C and V, with interferon-alpha receptor complex.
  Journal
Virology 306:135-46 (2003)
DOI:10.1016/S0042-6822(02)00026-0
Reference
PMID:12804771
  Authors
Takeuchi K, Kadota SI, Takeda M, Miyajima N, Nagata K
  Title
Measles virus V protein blocks interferon (IFN)-alpha/beta but not IFN-gamma signaling by inhibiting STAT1 and STAT2 phosphorylation.
  Journal
FEBS Lett 545:177-82 (2003)
DOI:10.1016/S0014-5793(03)00528-3
Reference
PMID:12805463
  Authors
Palosaari H, Parisien JP, Rodriguez JJ, Ulane CM, Horvath CM
  Title
STAT protein interference and suppression of cytokine signal transduction by measles virus V protein.
  Journal
J Virol 77:7635-44 (2003)
DOI:10.1128/JVI.77.13.7635-7644.2003
Reference
PMID:14585342
  Authors
Shaffer JA, Bellini WJ, Rota PA
  Title
The C protein of measles virus inhibits the type I interferon response.
  Journal
Virology 315:389-97 (2003)
DOI:10.1016/S0042-6822(03)00537-3
Reference
PMID:16971451
  Authors
Carsillo T, Traylor Z, Choi C, Niewiesk S, Oglesbee M
  Title
hsp72, a host determinant of measles virus neurovirulence.
  Journal
J Virol 80:11031-9 (2006)
DOI:10.1128/JVI.01438-06
Reference
PMID:15914229
  Authors
Zhang X, Bourhis JM, Longhi S, Carsillo T, Buccellato M, Morin B, Canard B, Oglesbee M
  Title
Hsp72 recognizes a P binding motif in the measles virus N protein C-terminus.
  Journal
Virology 337:162-74 (2005)
DOI:10.1016/j.virol.2005.03.035
Reference
PMID:29712906
  Authors
Ke Z, Strauss JD, Hampton CM, Brindley MA, Dillard RS, Leon F, Lamb KM, Plemper RK, Wright ER
  Title
Promotion of virus assembly and organization by the measles virus matrix protein.
  Journal
Nat Commun 9:1736 (2018)
DOI:10.1038/s41467-018-04058-2
Reference
PMID:24155404
  Authors
Pfaller CK, Radeke MJ, Cattaneo R, Samuel CE
  Title
Measles virus C protein impairs production of defective copyback double-stranded viral RNA and activation of protein kinase R.
  Journal
J Virol 88:456-68 (2014)
DOI:10.1128/JVI.02572-13
Reference
PMID:17686838
  Authors
Sato H, Masuda M, Kanai M, Tsukiyama-Kohara K, Yoneda M, Kai C
  Title
Measles virus N protein inhibits host translation by binding to eIF3-p40.
  Journal
J Virol 81:11569-76 (2007)
DOI:10.1128/JVI.00570-07
Reference
PMID:19895323
  Authors
Sion-Vardy N, Lasarov I, Delgado B, Gopas J, Benharroch D, Ariad S
  Title
Measles virus: evidence for association with lung cancer.
  Journal
Exp Lung Res 35:701-12 (2009)
DOI:10.3109/01902140902853176
Reference
PMID:16140759
  Authors
Chen M, Cortay JC, Logan IR, Sapountzi V, Robson CN, Gerlier D
  Title
Inhibition of ubiquitination and stabilization of human ubiquitin E3 ligase PIRH2 by measles virus phosphoprotein.
  Journal
J Virol 79:11824-36 (2005)
DOI:10.1128/JVI.79.18.11824-11836.2005
Reference
PMID:16699046
  Authors
Cruz CD, Palosaari H, Parisien JP, Devaux P, Cattaneo R, Ouchi T, Horvath CM
  Title
Measles virus V protein inhibits p53 family member p73.
  Journal
J Virol 80:5644-50 (2006)
DOI:10.1128/JVI.02400-05
Reference
PMID:10756053
  Authors
Servet-Delprat C, Vidalain PO, Azocar O, Le Deist F, Fischer A, Rabourdin-Combe C
  Title
Consequences of Fas-mediated human dendritic cell apoptosis induced by measles virus.
  Journal
J Virol 74:4387-93 (2000)
DOI:10.1128/JVI.74.9.4387-4393.2000
Reference
PMID:20601611
  Authors
Kushwah R, Hu J
  Title
Dendritic cell apoptosis: regulation of tolerance versus immunity.
  Journal
J Immunol 185:795-802 (2010)
DOI:10.4049/jimmunol.1000325
Reference
PMID:10590149
  Authors
Vidalain PO, Azocar O, Lamouille B, Astier A, Rabourdin-Combe C, Servet-Delprat C
  Title
Measles virus induces functional TRAIL production by human dendritic cells.
  Journal
J Virol 74:556-9 (2000)
DOI:10.1128/JVI.74.1.556-559.2000
Reference
PMID:11846228
  Authors
Vidalain PO, Azocar O, Rabourdin-Combe C, Servet-Delprat C
  Title
Measle virus-infected dendritic cells develop immunosuppressive and cytotoxic activities.
  Journal
Immunobiology 204:629-38 (2001)
DOI:10.1078/0171-2985-00102
Reference
PMID:10423127
  Authors
Engelking O, Fedorov LM, Lilischkis R, ter Meulen V, Schneider-Schaulies S
  Title
Measles virus-induced immunosuppression in vitro is associated with deregulation of G1 cell cycle control proteins.
  Journal
J Gen Virol 80 ( Pt 7):1599-608 (1999)
DOI:10.1099/0022-1317-80-7-1599
Reference
PMID:30510918
  Authors
Fan Y, Sanyal S, Bruzzone R
  Title
Breaking Bad: How Viruses Subvert the Cell Cycle.
  Journal
Front Cell Infect Microbiol 8:396 (2018)
DOI:10.3389/fcimb.2018.00396
Reference
PMID:20636817
  Authors
Griffin DE
  Title
Measles virus-induced suppression of immune responses.
  Journal
Immunol Rev 236:176-89 (2010)
DOI:10.1111/j.1600-065X.2010.00925.x
Reference
PMID:11385511
  Authors
Avota E, Avots A, Niewiesk S, Kane LP, Bommhardt U, ter Meulen V, Schneider-Schaulies S
  Title
Disruption of Akt kinase activation is important for immunosuppression induced by measles virus.
  Journal
Nat Med 7:725-31 (2001)
DOI:10.1038/89106
Reference
PMID:15308747
  Authors
Avota E, Muller N, Klett M, Schneider-Schaulies S
  Title
Measles virus interacts with and alters signal transduction in T-cell lipid rafts.
  Journal
J Virol 78:9552-9 (2004)
DOI:10.1128/JVI.78.17.9552-9559.2004
Reference
PMID:16963735
  Authors
Yanagi Y, Takeda M, Ohno S
  Title
Measles virus: cellular receptors, tropism and pathogenesis.
  Journal
J Gen Virol 87:2767-79 (2006)
DOI:10.1099/vir.0.82221-0
Reference
PMID:16237742
  Authors
Kerdiles YM, Sellin CI, Druelle J, Horvat B
  Title
Immunosuppression caused by measles virus: role of viral proteins.
  Journal
Rev Med Virol 16:49-63 (2006)
DOI:10.1002/rmv.486
Related
pathway
hsa04110  Cell cycle
hsa04115  p53 signaling pathway
hsa04120  Ubiquitin mediated proteolysis
hsa04210  Apoptosis
hsa04620  Toll-like receptor signaling pathway
hsa04622  RIG-I-like receptor signaling pathway
hsa04630  JAK-STAT signaling pathway
hsa04658  Th1 and Th2 cell differentiation
hsa04660  T cell receptor signaling pathway
KO pathway
ko05162   
LinkDB

DBGET integrated database retrieval system