KEGG PATHWAY: mcc05164

PATHWAY: mcc05164

Entry

mcc05164 Pathway

Name

Influenza A - Macaca mulatta (rhesus monkey)

Description

Influenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains that cause pandemics arise from avian influenza virus by genetic reassortment among influenza viruses and two surface glycoproteins HA and NA form the basis of serologically distinct virus types. The innate immune system recognizes invaded virus through multiple mechanisms. Viral non-structural NS1 protein is a multifunctional virulence factor that interfere IFN-mediated antiviral response. It inhibits IFN production by blocking activation of transcription factors such as NF-kappa B, IRF3 and AP1. NS1 further inhibits the activation of IFN-induced antiviral genes. PB1-F2 protein is another virulence factor that induce apoptosis of infected cells, which results in life-threatening bronchiolitis.

Class

Human Diseases; Infectious diseases

Pathway map

mcc05164

Influenza A

Organism

Macaca mulatta (rhesus monkey) [GN:mcc]

Gene

698352	PRSS2; protease, serine, 2 (trypsin 2) [KO:K01312] [EC:3.4.21.4]
699238	PRSS2; protease, serine, 2 (trypsin 2) [KO:K01312] [EC:3.4.21.4]
698729	PRSS1; protease, serine, 1 (trypsin 1) [KO:K01312] [EC:3.4.21.4]
698983	PRSS1; protease, serine, 1 (trypsin 1) [KO:K01312] [EC:3.4.21.4]
716882	trypsin-3-like; K01312 trypsin [EC:3.4.21.4] [KO:K01312] [EC:3.4.21.4]
715138	transmembrane protease serine 2-like; K09633 transmembrane protease, serine 2 [KO:K09633]
704604	TMPRSS4; transmembrane protease, serine 4 [KO:K09635]
712265	OAS1; 2'-5'-oligoadenylate synthetase 1, 40/46kDa [KO:K14216]
712401	OAS2; 2'-5'-oligoadenylate synthetase 2, 69/71kDa [KO:K14216]
712342	OAS3; 2'-5'-oligoadenylate synthetase 3, 100kDa [KO:K14216]
715647	RNASEL; ribonuclease L (2',5'-oligoisoadenylate synthetase-dependent) [KO:K01165]
718890	dnaJ homolog subfamily B member 1-like; K09507 DnaJ homolog subfamily B member 1 [KO:K09507]
695757	DNAJC3; DnaJ (Hsp40) homolog, subfamily C, member 3 [KO:K09523]
716633	heat shock 70 kDa protein 1-like; K03283 heat shock 70kDa protein 1/8 [KO:K03283]
707989	HSPA8; heat shock 70kDa protein 8 [KO:K03283]
677690	HSPA1B; heat shock 70kDa protein 1B [KO:K03283]
100424244	heat shock cognate 70 kDa protein 2-like; K03283 heat shock 70kDa protein 1/8 [KO:K03283]
703325	EIF2AK1; eukaryotic translation initiation factor 2-alpha kinase 1 [KO:K16194] [EC:2.7.11.1]
708912	EIF2AK2; eukaryotic translation initiation factor 2-alpha kinase 2 [KO:K16195] [EC:2.7.11.1]
699575	EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
100428309	EIF2AK4; eukaryotic translation initiation factor 2 alpha kinase 4 [KO:K16196] [EC:2.7.11.1]
710150	EIF2S1; eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa [KO:K03237]
705195	MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
693914	MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
715745	MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
715794	MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
718976	mitogen-activated protein kinase 14-like; K04441 p38 MAP kinase [EC:2.7.11.24] [KO:K04441] [EC:2.7.11.24]
719085	mitogen-activated protein kinase 13-like; K04441 p38 MAP kinase [EC:2.7.11.24] [KO:K04441] [EC:2.7.11.24]
718155	MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
710077	dual specificity mitogen-activated protein kinase kinase 7-like; K04431 mitogen-activated protein kinase kinase 7 [EC:2.7.12.2] [KO:K04431] [EC:2.7.12.2]
699736	MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
711115	MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
716452	JUN; jun proto-oncogene [KO:K04448]
704638	DDX58; DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 [KO:K12646] [EC:3.6.3.14]
702024	IFIH1; interferon induced with helicase C domain 1 [KO:K12647] [EC:3.6.4.13]
717616	MAVS; mitochondrial antiviral signaling protein [KO:K12648]
703981	NLRX1; NLR family member X1 [KO:K12653]
704683	IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
694844	NFKBIB; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, beta [KO:K02581]
695335	NFKBIA; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha [KO:K04734]
710324	NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
715919	RELA; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
712588	e3 ubiquitin/ISG15 ligase TRIM25-like; K10652 tripartite motif-containing protein 25 [KO:K10652]
574378	TLR3; toll-like receptor 3 [KO:K05401]
574294	TICAM1; toll-like receptor adaptor molecule 1 [KO:K05842]
717427	TBK1; TANK-binding kinase 1 [KO:K05410] [EC:2.7.11.10]
695607	IKBKE; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon [KO:K07211] [EC:2.7.11.10]
718970	IRF3; interferon regulatory factor 3 [KO:K05411]
706258	EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
704331	CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
707310	PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [KO:K02649]
719367	PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
722027	PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
698996	PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
698857	PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
716098	PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
709959	PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
714717	AKT3; v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma) [KO:K04456] [EC:2.7.11.1]
697747	AKT1; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
700591	AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
574360	TLR4; toll-like receptor 4 [KO:K10160]
574291	TLR7; toll-like receptor 7 [KO:K05404]
696494	MYD88; myeloid differentiation primary response gene (88) [KO:K04729]
700568	IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
699578	IRF7; interferon regulatory factor 7 [KO:K09447]
700193	IL1A; interleukin 1, alpha [KO:K04383]
704701	IL1B; interleukin 1, beta [KO:K04519]
705819	IL6; interleukin 6 (interferon, beta 2) [KO:K05405]
703205	IL12A; interleukin 12A (natural killer cell stimulatory factor 1, cytotoxic lymphocyte maturation factor 1, p35) [KO:K05406]
694747	IL12B; interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40) [KO:K05425]
715467	TNF; tumor necrosis factor [KO:K03156]
613028	IL8; interleukin 8 [KO:K10030]
574138	CCL2; chemokine (C-C motif) ligand 2 [KO:K14624]
574178	CCL5; chemokine (C-C motif) ligand 5 [KO:K12499]
574243	CXCL10; chemokine (C-X-C motif) ligand 10 [KO:K12671]
712280	ICAM1; intercellular adhesion molecule 1 [KO:K06490]
709948	IFNA2; interferon, alpha 2 [KO:K05414]
709755	IFNA8; interferon, alpha 8 [KO:K05414]
710707	interferon alpha-6-like; K05414 interferon alpha [KO:K05414]
710751	interferon alpha-17-like; K05414 interferon alpha [KO:K05414]
694631	interferon alpha-1/13-like; K05414 interferon alpha [KO:K05414]
710487	IFNA14; interferon, alpha 14 [KO:K05414]
710528	interferon alpha-1/13-like; K05414 interferon alpha [KO:K05414]
710568	interferon alpha-4-like; K05414 interferon alpha [KO:K05414]
710654	IFNA10; interferon, alpha 10 [KO:K05414]
711252	interferon alpha-21-like; K05414 interferon alpha [KO:K05414]
709559	IFNA13; interferon, alpha 13 [KO:K05414]
711414	IFNB1; interferon, beta 1, fibroblast [KO:K05415]
699604	IFNAR1; interferon (alpha, beta and omega) receptor 1 [KO:K05130]
699726	IFNAR2; interferon (alpha, beta and omega) receptor 2 [KO:K05131]
677689	JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
574130	TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
693650	STAT1; signal transducer and activator of transcription 1, 91kDa [KO:K11220]
712694	STAT2; signal transducer and activator of transcription 2, 113kDa [KO:K11221]
715335	interferon regulatory factor 9; K04693 interferon regulatory factor 9 [KO:K04693]
715680	SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
715186	MX1; myxovirus (influenza virus) resistance 1, interferon-inducible protein p78 (mouse) [KO:K14754]
718759	ADAR; adenosine deaminase, RNA-specific [KO:K12968] [EC:3.5.4.-]
700379	PML; promyelocytic leukemia [KO:K10054]
574282	IFNG; interferon, gamma [KO:K04687]
100423877	IFNGR1; interferon gamma receptor 1 [KO:K05132]
699489	IFNGR2; interferon gamma receptor 2 (interferon gamma transducer 1) [KO:K05133]
694184	JAK2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
710761	CIITA; class II, major histocompatibility complex, transactivator [KO:K08060]
692100	MAMU-DRB1; MHC class II antigen [KO:K06752]
717870	MAMU-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]
717969	MAMU-DPB; major histocompatibility complex, class II, DP beta [KO:K06752]
705588	HLA class II histocompatibility antigen; K06752 major histocompatibility complex, class II [KO:K06752]
717947	MAMU-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]
717992	MAMU-DPA; major histocompatibility complex, class II, DP alpha [KO:K06752]
717623	HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1-like [KO:K06752]
717702	MAMU-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]
100187587	MAMU-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]
720582	MAMU-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]
716823	MAMU-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]
100429857	MAMU-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]
100428228	MAMU-DRB5; HLA class II histocompatibility antigen, DRB1-4 beta chain [KO:K06752]
701278	NLRP3; NLR family, pyrin domain containing 3 [KO:K12800]
713563	PYCARD; PYD and CARD domain containing [KO:K12799]
706568	CASP1; caspase 1, apoptosis-related cysteine peptidase [KO:K01370] [EC:3.4.22.36]
574151	IL18; interleukin 18 (interferon-gamma-inducing factor) [KO:K05482]
694451	TNFSF10; tumor necrosis factor (ligand) superfamily, member 10 [KO:K04721]
716650	tumor necrosis factor receptor superfamily member 10B-like; K04722 tumor necrosis factor receptor superfamily member 10 [KO:K04722]
716826	TNFRSF10A; tumor necrosis factor receptor superfamily, member 10a [KO:K04722]
716901	TNFRSF10D; tumor necrosis factor receptor superfamily, member 10d, decoy with truncated death domain [KO:K04722]
719398	tumor necrosis factor receptor superfamily member 10B-like; K04722 tumor necrosis factor receptor superfamily member 10 [KO:K04722]
574159	FASLG; Fas ligand (TNF superfamily, member 6) [KO:K04389]
574332	FAS; Fas (TNF receptor superfamily, member 6) [KO:K04390]
722033	TNFRSF1A; tumor necrosis factor receptor superfamily, member 1A [KO:K03158]
710045	VDAC1; voltage-dependent anion channel 1 [KO:K05862]
705449	cytochrome c-like; K08738 cytochrome c [KO:K08738]
695875	cytochrome c-like; K08738 cytochrome c [KO:K08738]
716056	cytochrome c-like; K08738 cytochrome c [KO:K08738]
711309	cytochrome c-like; K08738 cytochrome c [KO:K08738]
694977	cytochrome c pseudogene; K08738 cytochrome c [KO:K08738]
698225	cytochrome c-like; K08738 cytochrome c [KO:K08738]
701246	cytochrome c-like; K08738 cytochrome c [KO:K08738]
699951	cytochrome c-like; K08738 cytochrome c [KO:K08738]
702488	cytochrome c-like; K08738 cytochrome c [KO:K08738]
100425223	CYCS; cytochrome c, somatic [KO:K08738]
694544	CASP9; caspase 9, apoptosis-related cysteine peptidase [KO:K04399] [EC:3.4.22.62]
713114	GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
692082	KPNA1; karyopherin alpha 1 (importin alpha 5) [KO:K15042]
100430009	KPNA2; karyopherin alpha 2 (RAG cohort 1, importin alpha 1) [KO:K15043]
715233	DDX39B; DEAD (Asp-Glu-Ala-Asp) box polypeptide 39B [KO:K12812] [EC:3.6.4.13]
718063	XPO1; exportin 1 (CRM1 homolog, yeast) [KO:K14290]
708910	AGFG1; ArfGAP with FG repeats 1 [KO:K15044]
694725	RAF1; v-raf-1 murine leukemia viral oncogene homolog 1 [KO:K04366] [EC:2.7.11.1]
710415	MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
721821	MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
698569	MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
708938	MAPK3; mitogen-activated protein kinase 3-like [KO:K04371] [EC:2.7.11.24]
708720	RSAD2; radical S-adenosyl methionine domain containing 2 [KO:K15045]
709287	farnesyl pyrophosphate synthase-like; K00787 farnesyl diphosphate synthase [EC:2.5.1.1 2.5.1.10] [KO:K00787] [EC:2.5.1.10 2.5.1.1]
700393	actin; K05692 actin beta/gamma 1 [KO:K05692]
713687	ACTG1; actin, gamma 1 [KO:K05692]
574285	ACTB; actin, beta [KO:K05692]
100428865	actin; K05692 actin beta/gamma 1 [KO:K05692]
714152	IVNS1ABP; influenza virus NS1A binding protein [KO:K15046]
708119	CPSF4; cleavage and polyadenylation specific factor 4, 30kDa [KO:K14404]
713572	polyadenylate-binding protein 2-like; K14396 polyadenylate-binding protein 2 [KO:K14396]
721624	embryonic polyadenylate-binding protein 2-like; K14396 polyadenylate-binding protein 2 [KO:K14396]
711697	embryonic polyadenylate-binding protein 2-like; K14396 polyadenylate-binding protein 2 [KO:K14396]
718420	NXF1; nuclear RNA export factor 1 [KO:K14284]
706029	nuclear RNA export factor 2-like; K14284 nuclear RNA export factor 1/2 [KO:K14284]
706140	nuclear RNA export factor 2-like; K14284 nuclear RNA export factor 1/2 [KO:K14284]
695351	NXF3; nuclear RNA export factor 3 [KO:K14284]
704593	NXT2; nuclear transport factor 2-like export factor 2 [KO:K14285]
711846	NXT1; NTF2-like export factor 1 [KO:K14285]
696706	RAE1; RAE1 RNA export 1 homolog (S. pombe) [KO:K14298]
706123	AXL; uncharacterized LOC706123 [KO:K15047]
717608	nuclear pore complex protein Nup98-Nup96-like; K14297 nuclear pore complex protein Nup98-Nup96 [KO:K14297]
715813	FURIN; furin (paired basic amino acid cleaving enzyme) [KO:K01349] [EC:3.4.21.75]
698586	TMPRSS13; transmembrane protease, serine 13 [KO:K09643]
703891	PLG; plasminogen [KO:K01315] [EC:3.4.21.7]

Compound

C00027	Hydrogen peroxide
C00080	H+
C05981	Phosphatidylinositol-3,4,5-trisphosphate
C18990	PB1-F2

Reference

PMID:19782761

Authors

Ehrhardt C, Seyer R, Hrincius ER, Eierhoff T, Wolff T, Ludwig S

Title

Interplay between influenza A virus and the innate immune signaling.

Journal

Microbes Infect 12:81-7 (2010)

Reference

PMID:20020828

Authors

Hale BG, Albrecht RA, Garcia-Sastre A

Title

Innate immune evasion strategies of influenza viruses.

Journal

Future Microbiol 5:23-41 (2010)

Reference

PMID:19420020

Authors

Ludwig S

Title

Targeting cell signalling pathways to fight the flu: towards a paradigm change in anti-influenza therapy.

Journal

J Antimicrob Chemother 64:1-4 (2009)

Reference

PMID:18049471

Authors

von Itzstein M

Title

The war against influenza: discovery and development of sialidase inhibitors.

Journal

Nat Rev Drug Discov 6:967-74 (2007)

Reference

PMID:16494716

Authors

Garcia-Sastre A

Title

Antiviral response in pandemic influenza viruses.

Journal

Emerg Infect Dis 12:44-7 (2006)

Reference

PMID:18980544

Authors

Ichinohe T, Iwasaki A, Hasegawa H

Title

Innate sensors of influenza virus: clues to developing better intranasal vaccines.

Journal

Expert Rev Vaccines 7:1435-45 (2008)

Reference

PMID:19864182

Authors

Peiris JS, Cheung CY, Leung CY, Nicholls JM

Title

Innate immune responses to influenza A H5N1: friend or foe?

Journal

Trends Immunol 30:574-84 (2009)

Reference

PMID:18588994

Authors

Thanh TT, van Doorn HR, de Jong MD

Title

Human H5N1 influenza: current insight into pathogenesis.

Journal

Int J Biochem Cell Biol 40:2671-4 (2008)

Reference

PMID:17944269

Authors

Neumann G, Shinya K, Kawaoka Y

Title

Molecular pathogenesis of H5N1 influenza virus infections.

Journal

Antivir Ther 12:617-26 (2007)

Reference

PMID:17213831

Authors

La Gruta NL, Kedzierska K, Stambas J, Doherty PC

Title

A question of self-preservation: immunopathology in influenza virus infection.

Journal

Immunol Cell Biol 85:85-92 (2007)

Reference

PMID:19481124

Authors

Nayak DP, Balogun RA, Yamada H, Zhou ZH, Barman S

Title

Influenza virus morphogenesis and budding.

Journal

Virus Res 143:147-61 (2009)

Reference

PMID:17072332

Authors

Hiscott J, Nguyen TL, Arguello M, Nakhaei P, Paz S

Title

Manipulation of the nuclear factor-kappaB pathway and the innate immune response by viruses.

Journal

Oncogene 25:6844-67 (2006)

Reference

PMID:19290913

Authors

Ehrhardt C, Ludwig S

Title

A new player in a deadly game: influenza viruses and the PI3K/Akt signalling pathway.

Journal

Cell Microbiol 11:863-71 (2009)

Reference

PMID:21147034

Authors

Pang IK, Iwasaki A

Title

Inflammasomes as mediators of immunity against influenza virus.

Journal

Trends Immunol 32:34-41 (2011)

Reference

PMID:17267598

Authors

Satterly N, Tsai PL, van Deursen J, Nussenzveig DR, Wang Y, Faria PA, Levay A, Levy DE, Fontoura BM

Title

Influenza virus targets the mRNA export machinery and the nuclear pore complex.

Journal

Proc Natl Acad Sci U S A 104:1853-8 (2007)

Reference

PMID:16882036

Authors

Ehrhardt C, Marjuki H, Wolff T, Nurnberg B, Planz O, Pleschka S, Ludwig S

Title

Bivalent role of the phosphatidylinositol-3-kinase (PI3K) during influenza virus infection and host cell defence.

Journal

Cell Microbiol 8:1336-48 (2006)

Reference

PMID:15502848

Authors

Sarkar SN, Peters KL, Elco CP, Sakamoto S, Pal S, Sen GC

Title

Novel roles of TLR3 tyrosine phosphorylation and PI3 kinase in double-stranded RNA signaling.

Journal

Nat Struct Mol Biol 11:1060-7 (2004)

Reference

PMID:11907320

Authors

Portela A, Digard P

Title

The influenza virus nucleoprotein: a multifunctional RNA-binding protein pivotal to virus replication.

Journal

J Gen Virol 83:723-34 (2002)

Reference

PMID:9060654

Authors

Avalos RT, Yu Z, Nayak DP

Title

Association of influenza virus NP and M1 proteins with cellular cytoskeletal elements in influenza virus-infected cells.

Journal

J Virol 71:2947-58 (1997)

Reference

PMID:20629046

Authors

Bertram S, Glowacka I, Steffen I, Kuhl A, Pohlmann S

Title

Novel insights into proteolytic cleavage of influenza virus hemagglutinin.

Journal

Rev Med Virol 20:298-310 (2010)

KO pathway

ko05164

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Pathway (1)   
   BioSystems (1)   
Genome (1)   
   KEGG GENOME (1)   
Gene (175)   
   KEGG GENES (175)   
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