KEGG   PATHWAY: mmu05162
mmu05162                    Pathway                                

Measles - Mus musculus (mouse)
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
mmu05162  Measles

Mus musculus (mouse) [GN:mmu]
17221  Cd46; CD46 antigen, complement regulatory protein [KO:K04007]
17698  Msn; moesin [KO:K05763]
27218  Slamf1; signaling lymphocytic activation molecule family member 1 [KO:K06536]
170776  Cd209c; CD209c antigen [KO:K06563]
170779  Cd209d; CD209d antigen [KO:K06563]
170780  Cd209e; CD209e antigen [KO:K06563]
170786  Cd209a; CD209a antigen [KO:K06563]
69165  Cd209b; CD209b antigen [KO:K06563]
69142  Cd209f; CD209f antigen [KO:K06563]
70192  Cd209g; CD209g antigen [KO:K06563]
230073  Ddx58; DEAD/H box helicase 58 [KO:K12646] [EC:]
71586  Ifih1; interferon induced with helicase C domain 1 [KO:K12647] [EC:]
228607  Mavs; mitochondrial antiviral signaling protein [KO:K12648]
22031  Traf3; TNF receptor-associated factor 3 [KO:K03174]
56489  Ikbke; inhibitor of kappaB kinase epsilon [KO:K07211] [EC:]
56480  Tbk1; TANK-binding kinase 1 [KO:K05410] [EC:]
54131  Irf3; interferon regulatory factor 3 [KO:K05411]
12675  Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:]
16150  Ikbkb; inhibitor of kappaB kinase beta [KO:K07209] [EC:]
16151  Ikbkg; inhibitor of kappaB kinase gamma [KO:K07210]
18036  Nfkbib; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, beta [KO:K02581]
18035  Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha [KO:K04734]
18033  Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580]
19697  Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
170743  Tlr7; toll-like receptor 7 [KO:K05404]
81897  Tlr9; toll-like receptor 9 [KO:K10161]
17874  Myd88; myeloid differentiation primary response gene 88 [KO:K04729]
16179  Irak1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:]
266632  Irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:]
54123  Irf7; interferon regulatory factor 7 [KO:K09447]
15962  Ifna1; interferon alpha 1 [KO:K05414]
15965  Ifna2; interferon alpha 2 [KO:K05414]
15967  Ifna4; interferon alpha 4 [KO:K05414]
15968  Ifna5; interferon alpha 5 [KO:K05414]
15969  Ifna6; interferon alpha 6 [KO:K05414]
15970  Ifna7; interferon alpha 7 [KO:K05414]
15972  Ifna9; interferon alpha 9 [KO:K05414]
15964  Ifna11; interferon alpha 11 [KO:K05414]
242519  Ifna12; interferon alpha 12 [KO:K05414]
230396  Ifna13; interferon alpha 13 [KO:K05414]
404549  Ifna14; interferon alpha 14 [KO:K05414]
15974  Ifnab; interferon alpha B [KO:K05414]
242517  Ifna15; interferon alpha 15 [KO:K05414]
230398  Ifna16; interferon alpha 16 [KO:K05414]
15977  Ifnb1; interferon beta 1, fibroblast [KO:K05415]
24088  Tlr2; toll-like receptor 2 [KO:K10159]
21898  Tlr4; toll-like receptor 4 [KO:K10160]
22034  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:]
12995  Csnk2a1; casein kinase 2, alpha 1 polypeptide [KO:K03097] [EC:]
13000  Csnk2a2; casein kinase 2, alpha prime polypeptide [KO:K03097] [EC:]
13001  Csnk2b; casein kinase 2, beta polypeptide [KO:K03115]
21929  Tnfaip3; tumor necrosis factor, alpha-induced protein 3 [KO:K11859] [EC:]
26409  Map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:]
68652  Tab2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
26419  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:]
26420  Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:]
26414  Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:]
16476  Jun; jun proto-oncogene [KO:K04448]
14281  Fos; FBJ osteosarcoma oncogene [KO:K04379]
16175  Il1a; interleukin 1 alpha [KO:K04383]
16176  Il1b; interleukin 1 beta [KO:K04519]
16193  Il6; interleukin 6 [KO:K05405]
16159  Il12a; interleukin 12a [KO:K05406]
16160  Il12b; interleukin 12b [KO:K05425]
15975  Ifnar1; interferon (alpha and beta) receptor 1 [KO:K05130]
15976  Ifnar2; interferon (alpha and beta) receptor 2 [KO:K05131]
14694  Rack1; receptor for activated C kinase 1 [KO:K14753]
16451  Jak1; Janus kinase 1 [KO:K11217] [EC:]
54721  Tyk2; tyrosine kinase 2 [KO:K11219] [EC:]
20846  Stat1; signal transducer and activator of transcription 1 [KO:K11220]
20847  Stat2; signal transducer and activator of transcription 2 [KO:K11221]
16391  Irf9; interferon regulatory factor 9 [KO:K04693]
246730  Oas1a; 2'-5' oligoadenylate synthetase 1A [KO:K14216] [EC:]
246728  Oas2; 2'-5' oligoadenylate synthetase 2 [KO:K14216] [EC:]
246727  Oas3; 2'-5' oligoadenylate synthetase 3 [KO:K14216] [EC:]
23961  Oas1b; 2'-5' oligoadenylate synthetase 1B [KO:K14216] [EC:]
23960  Oas1g; 2'-5' oligoadenylate synthetase 1G [KO:K14216] [EC:]
56417  Adar; adenosine deaminase, RNA-specific [KO:K12968] [EC:]
17858  Mx2; MX dynamin-like GTPase 2 [KO:K14754]
17857  Mx1; MX dynamin-like GTPase 1 [KO:K14754]
15467  Eif2ak1; eukaryotic translation initiation factor 2 alpha kinase 1 [KO:K16194] [EC:]
19106  Eif2ak2; eukaryotic translation initiation factor 2-alpha kinase 2 [KO:K16195] [EC:]
13666  Eif2ak3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:]
27103  Eif2ak4; eukaryotic translation initiation factor 2 alpha kinase 4 [KO:K16196] [EC:]
56382  Rab9; RAB9, member RAS oncogene family [KO:K07899]
319642  Rab9b; RAB9B, member RAS oncogene family [KO:K07900]
15481  Hspa8; heat shock protein 8 [KO:K03283]
15482  Hspa1l; heat shock protein 1-like [KO:K03283]
193740  Hspa1a; heat shock protein 1A [KO:K03283]
15512  Hspa2; heat shock protein 2 [KO:K03283]
15511  Hspa1b; heat shock protein 1B [KO:K03283]
68135  Eif3h; eukaryotic translation initiation factor 3, subunit H [KO:K03247]
13665  Eif2s1; eukaryotic translation initiation factor 2, subunit 1 alpha [KO:K03237]
68098  Rchy1; ring finger and CHY zinc finger domain containing 1 [KO:K10144] [EC:]
22059  Trp53; transformation related protein 53 [KO:K04451]
22062  Trp73; transformation related protein 73 [KO:K10148]
170770  Bbc3; BCL2 binding component 3 [KO:K10132]
14103  Fasl; Fas ligand (TNF superfamily, member 6) [KO:K04389]
14102  Fas; Fas (TNF receptor superfamily member 6) [KO:K04390]
71609  Tradd; TNFRSF1A-associated via death domain [KO:K03171]
14082  Fadd; Fas (TNFRSF6)-associated via death domain [KO:K02373]
12370  Casp8; caspase 8 [KO:K04398] [EC:]
12122  Bid; BH3 interacting domain death agonist [KO:K04726]
12028  Bax; BCL2-associated X protein [KO:K02159]
12018  Bak1; BCL2-antagonist/killer 1 [KO:K14021]
12043  Bcl2; B cell leukemia/lymphoma 2 [KO:K02161]
12048  Bcl2l1; BCL2-like 1 [KO:K04570]
12015  Bad; BCL2-associated agonist of cell death [KO:K02158]
13063  Cycs; cytochrome c, somatic [KO:K08738]
13067  Cyct; cytochrome c, testis [KO:K08738]
11783  Apaf1; apoptotic peptidase activating factor 1 [KO:K02084]
12371  Casp9; caspase 9 [KO:K04399] [EC:]
12367  Casp3; caspase 3 [KO:K02187] [EC:]
12576  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
12443  Ccnd1; cyclin D1 [KO:K04503]
12444  Ccnd2; cyclin D2 [KO:K10151]
12445  Ccnd3; cyclin D3 [KO:K10152]
12447  Ccne1; cyclin E1 [KO:K06626]
12448  Ccne2; cyclin E2 [KO:K06626]
12567  Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:]
12571  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:]
12566  Cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:]
12500  Cd3d; CD3 antigen, delta polypeptide [KO:K06450]
12501  Cd3e; CD3 antigen, epsilon polypeptide [KO:K06451]
12502  Cd3g; CD3 antigen, gamma polypeptide [KO:K06452]
12487  Cd28; CD28 antigen [KO:K06470]
16183  Il2; interleukin 2 [KO:K05429]
16184  Il2ra; interleukin 2 receptor, alpha chain [KO:K05068]
16185  Il2rb; interleukin 2 receptor, beta chain [KO:K05069]
16186  Il2rg; interleukin 2 receptor, gamma chain [KO:K05070]
18709  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
18708  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
18710  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
18706  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:]
18707  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:]
74769  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:]
208650  Cblb; Casitas B-lineage lymphoma b [KO:K22517] [EC:]
11651  Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:]
11652  Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:]
23797  Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:]
56637  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:]
16453  Jak3; Janus kinase 3 [KO:K11218] [EC:]
20848  Stat3; signal transducer and activator of transcription 3 [KO:K04692]
20850  Stat5a; signal transducer and activator of transcription 5A [KO:K11223]
20851  Stat5b; signal transducer and activator of transcription 5B [KO:K11224]
14130  Fcgr2b; Fc receptor, IgG, low affinity 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)
mmu04110  Cell cycle
mmu04115  p53 signaling pathway
mmu04120  Ubiquitin mediated proteolysis
mmu04210  Apoptosis
mmu04620  Toll-like receptor signaling pathway
mmu04622  RIG-I-like receptor signaling pathway
mmu04630  JAK-STAT signaling pathway
mmu04658  Th1 and Th2 cell differentiation
mmu04660  T cell receptor signaling pathway
KO pathway

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