KEGG   PATHWAY: hsa05162
hsa05162                    Pathway                                
Measles - Homo sapiens (human)
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.
Human Diseases; Infectious disease: viral
Pathway map
hsa05162  Measles

nt06114  PI3K signaling (viruses)
nt06121  TLR signaling (viruses and bacteria)
nt06122  IFN signaling (viruses)
nt06133  RLR signaling (viruses)
nt06138  PKR-eIF2alpha signaling (viruses)
nt06140  Transcription (viruses)
nt06169  Measles virus (MV)
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
H00394  Measles
D03305  Interferon alfa (NAMALWA) (JP18)
Homo sapiens (human) [GN:hsa]
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:]
64135  IFIH1; interferon induced with helicase C domain 1 [KO:K12647] [EC:]
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:]
29110  TBK1; TANK binding kinase 1 [KO:K05410] [EC:]
3661  IRF3; interferon regulatory factor 3 [KO:K05411]
1147  CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:]
3551  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:]
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:]
51135  IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:]
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:]
1457  CSNK2A1; casein kinase 2 alpha 1 [KO:K03097] [EC:]
1459  CSNK2A2; casein kinase 2 alpha 2 [KO:K03097] [EC:]
283106  CSNK2A3; casein kinase 2 alpha 3 [KO:K03097] [EC:]
1460  CSNK2B; casein kinase 2 beta [KO:K03115]
7128  TNFAIP3; TNF alpha induced protein 3 [KO:K11859] [EC:]
6885  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:]
23118  TAB2; TGF-beta activated kinase 1 (MAP3K7) binding protein 2 [KO:K04404]
5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:]
5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:]
5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:]
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:]
7297  TYK2; tyrosine kinase 2 [KO:K11219] [EC:]
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:]
4939  OAS2; 2'-5'-oligoadenylate synthetase 2 [KO:K14216] [EC:]
4940  OAS3; 2'-5'-oligoadenylate synthetase 3 [KO:K14216] [EC:]
103  ADAR; adenosine deaminase RNA specific [KO:K12968] [EC:]
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:]
5610  EIF2AK2; eukaryotic translation initiation factor 2 alpha kinase 2 [KO:K16195] [EC:]
9451  EIF2AK3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:]
440275  EIF2AK4; eukaryotic translation initiation factor 2 alpha kinase 4 [KO:K16196] [EC:]
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]
3306  HSPA2; heat shock protein family A (Hsp70) member 2 [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:]
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:]
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:]
836  CASP3; caspase 3 [KO:K02187] [EC:]
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:]
1021  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:]
1017  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:]
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:]
5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:]
5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:]
868  CBLB; Cbl proto-oncogene B [KO:K22517] [EC:]
207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:]
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:]
2932  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:]
3718  JAK3; Janus kinase 3 [KO:K11218] [EC:]
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]
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Schneider-Schaulies S, Schneider-Schaulies J
Measles virus-induced immunosuppression.
Curr Top Microbiol Immunol 330:243-69 (2009)
Hahm B
Hostile communication of measles virus with host innate immunity and dendritic cells.
Curr Top Microbiol Immunol 330:271-87 (2009)
Gerlier D, Valentin H
Measles virus interaction with host cells and impact on innate immunity.
Curr Top Microbiol Immunol 329:163-91 (2009)
Schneider-Schaulies S, Dittmer U
Silencing T cells or T-cell silencing: concepts in virus-induced immunosuppression.
J Gen Virol 87:1423-38 (2006)
Avota E, Gassert E, Schneider-Schaulies S
Cytoskeletal dynamics: concepts in measles virus replication and immunomodulation.
Viruses 3:102-17 (2011)
Jiang Y, Qin Y, Chen M
Host-Pathogen Interactions in Measles Virus Replication and Anti-Viral Immunity.
Viruses 8:E308 (2016)
Pfaller CK, Conzelmann KK
Measles virus V protein is a decoy substrate for IkappaB kinase alpha and prevents Toll-like receptor 7/9-mediated interferon induction.
J Virol 82:12365-73 (2008)
Yokota S, Okabayashi T, Yokosawa N, Fujii N
Measles virus P protein suppresses Toll-like receptor signal through up-regulation of ubiquitin-modifying enzyme A20.
FASEB J 22:74-83 (2008)
Delpeut S, Noyce RS, Siu RW, Richardson CD
Host factors and measles virus replication.
Curr Opin Virol 2:773-83 (2012)
Shah M, Anwar MA, Kim JH, Choi S
Advances in Antiviral Therapies Targeting Toll-like Receptors.
Expert Opin Investig Drugs 25:437-53 (2016)
Yokota S, Saito H, Kubota T, Yokosawa N, Amano K, Fujii N
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.
Virology 306:135-46 (2003)
Takeuchi K, Kadota SI, Takeda M, Miyajima N, Nagata K
Measles virus V protein blocks interferon (IFN)-alpha/beta but not IFN-gamma signaling by inhibiting STAT1 and STAT2 phosphorylation.
FEBS Lett 545:177-82 (2003)
Palosaari H, Parisien JP, Rodriguez JJ, Ulane CM, Horvath CM
STAT protein interference and suppression of cytokine signal transduction by measles virus V protein.
J Virol 77:7635-44 (2003)
Shaffer JA, Bellini WJ, Rota PA
The C protein of measles virus inhibits the type I interferon response.
Virology 315:389-97 (2003)
Carsillo T, Traylor Z, Choi C, Niewiesk S, Oglesbee M
hsp72, a host determinant of measles virus neurovirulence.
J Virol 80:11031-9 (2006)
Zhang X, Bourhis JM, Longhi S, Carsillo T, Buccellato M, Morin B, Canard B, Oglesbee M
Hsp72 recognizes a P binding motif in the measles virus N protein C-terminus.
Virology 337:162-74 (2005)
Ke Z, Strauss JD, Hampton CM, Brindley MA, Dillard RS, Leon F, Lamb KM, Plemper RK, Wright ER
Promotion of virus assembly and organization by the measles virus matrix protein.
Nat Commun 9:1736 (2018)
Pfaller CK, Radeke MJ, Cattaneo R, Samuel CE
Measles virus C protein impairs production of defective copyback double-stranded viral RNA and activation of protein kinase R.
J Virol 88:456-68 (2014)
Sato H, Masuda M, Kanai M, Tsukiyama-Kohara K, Yoneda M, Kai C
Measles virus N protein inhibits host translation by binding to eIF3-p40.
J Virol 81:11569-76 (2007)
Sion-Vardy N, Lasarov I, Delgado B, Gopas J, Benharroch D, Ariad S
Measles virus: evidence for association with lung cancer.
Exp Lung Res 35:701-12 (2009)
Chen M, Cortay JC, Logan IR, Sapountzi V, Robson CN, Gerlier D
Inhibition of ubiquitination and stabilization of human ubiquitin E3 ligase PIRH2 by measles virus phosphoprotein.
J Virol 79:11824-36 (2005)
Cruz CD, Palosaari H, Parisien JP, Devaux P, Cattaneo R, Ouchi T, Horvath CM
Measles virus V protein inhibits p53 family member p73.
J Virol 80:5644-50 (2006)
Servet-Delprat C, Vidalain PO, Azocar O, Le Deist F, Fischer A, Rabourdin-Combe C
Consequences of Fas-mediated human dendritic cell apoptosis induced by measles virus.
J Virol 74:4387-93 (2000)
Kushwah R, Hu J
Dendritic cell apoptosis: regulation of tolerance versus immunity.
J Immunol 185:795-802 (2010)
Vidalain PO, Azocar O, Lamouille B, Astier A, Rabourdin-Combe C, Servet-Delprat C
Measles virus induces functional TRAIL production by human dendritic cells.
J Virol 74:556-9 (2000)
Vidalain PO, Azocar O, Rabourdin-Combe C, Servet-Delprat C
Measle virus-infected dendritic cells develop immunosuppressive and cytotoxic activities.
Immunobiology 204:629-38 (2001)
Engelking O, Fedorov LM, Lilischkis R, ter Meulen V, Schneider-Schaulies S
Measles virus-induced immunosuppression in vitro is associated with deregulation of G1 cell cycle control proteins.
J Gen Virol 80 ( Pt 7):1599-608 (1999)
Fan Y, Sanyal S, Bruzzone R
Breaking Bad: How Viruses Subvert the Cell Cycle.
Front Cell Infect Microbiol 8:396 (2018)
Griffin DE
Measles virus-induced suppression of immune responses.
Immunol Rev 236:176-89 (2010)
Avota E, Avots A, Niewiesk S, Kane LP, Bommhardt U, ter Meulen V, Schneider-Schaulies S
Disruption of Akt kinase activation is important for immunosuppression induced by measles virus.
Nat Med 7:725-31 (2001)
Avota E, Muller N, Klett M, Schneider-Schaulies S
Measles virus interacts with and alters signal transduction in T-cell lipid rafts.
J Virol 78:9552-9 (2004)
Yanagi Y, Takeda M, Ohno S
Measles virus: cellular receptors, tropism and pathogenesis.
J Gen Virol 87:2767-79 (2006)
Kerdiles YM, Sellin CI, Druelle J, Horvat B
Immunosuppression caused by measles virus: role of viral proteins.
Rev Med Virol 16:49-63 (2006)
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

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