KEGG   PATHWAY: hsa05164Help
Entry
hsa05164                    Pathway                                

Name
Influenza A - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
hsa05164  Influenza A
hsa05164

Ortholog table
Disease
H00398  Influenza
H00399  Avian influenza
Organism
Homo sapiens (human) [GN:hsa]
Gene
5646  PRSS3; serine protease 3 [KO:K01312] [EC:3.4.21.4]
5645  PRSS2; serine protease 2 [KO:K01312] [EC:3.4.21.4]
5644  PRSS1; serine protease 1 [KO:K01312] [EC:3.4.21.4]
7113  TMPRSS2; transmembrane serine protease 2 [KO:K09633] [EC:3.4.21.-]
56649  TMPRSS4; transmembrane serine protease 4 [KO:K09635] [EC:3.4.21.-]
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]
6041  RNASEL; ribonuclease L [KO:K01165]
3337  DNAJB1; DnaJ heat shock protein family (Hsp40) member B1 [KO:K09507]
5611  DNAJC3; DnaJ heat shock protein family (Hsp40) member C3 [KO:K09523]
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]
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]
1965  EIF2S1; eukaryotic translation initiation factor 2 subunit alpha [KO:K03237]
5606  MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
5608  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
5600  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
6416  MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
5609  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
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]
1386  ATF2; activating transcription factor 2 [KO:K04450]
23586  DDX58; DExD/H-box helicase 58 [KO:K12646] [EC:3.6.3.14]
64135  IFIH1; interferon induced with helicase C domain 1 [KO:K12647] [EC:3.6.4.13]
57506  MAVS; mitochondrial antiviral signaling protein [KO:K12648]
79671  NLRX1; NLR family member X1 [KO:K12653]
3551  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
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]
7706  TRIM25; tripartite motif containing 25 [KO:K10652] [EC:2.3.2.27]
7098  TLR3; toll like receptor 3 [KO:K05401]
148022  TICAM1; toll like receptor adaptor molecule 1 [KO:K05842]
29110  TBK1; TANK binding kinase 1 [KO:K05410] [EC:2.7.11.10]
9641  IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
3661  IRF3; interferon regulatory factor 3 [KO:K05411]
1387  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
2033  EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
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]
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]
7099  TLR4; toll like receptor 4 [KO:K10160]
51284  TLR7; toll like receptor 7 [KO:K05404]
4615  MYD88; MYD88, innate immune signal transduction adaptor [KO:K04729]
51135  IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:2.7.11.1]
3665  IRF7; interferon regulatory factor 7 [KO:K09447]
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]
7124  TNF; tumor necrosis factor [KO:K03156]
3576  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
6347  CCL2; C-C motif chemokine ligand 2 [KO:K14624]
6352  CCL5; C-C motif chemokine ligand 5 [KO:K12499]
3627  CXCL10; C-X-C motif chemokine ligand 10 [KO:K12671]
3383  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
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]
3454  IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130]
3455  IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131]
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]
9021  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
4599  MX1; MX dynamin like GTPase 1 [KO:K14754]
103  ADAR; adenosine deaminase, RNA specific [KO:K12968] [EC:3.5.4.37]
5371  PML; promyelocytic leukemia [KO:K10054]
3458  IFNG; interferon gamma [KO:K04687]
3459  IFNGR1; interferon gamma receptor 1 [KO:K05132]
3460  IFNGR2; interferon gamma receptor 2 [KO:K05133]
3717  JAK2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
4261  CIITA; class II major histocompatibility complex transactivator [KO:K08060]
3108  HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]
3109  HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]
3111  HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]
3112  HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]
3113  HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]
3115  HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]
3117  HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]
3118  HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]
3119  HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]
3122  HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]
3123  HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]
3125  HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]
3126  HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]
3127  HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]
114548  NLRP3; NLR family pyrin domain containing 3 [KO:K12800]
29108  PYCARD; PYD and CARD domain containing [KO:K12799]
834  CASP1; caspase 1 [KO:K01370] [EC:3.4.22.36]
3606  IL18; interleukin 18 [KO:K05482]
90865  IL33; interleukin 33 [KO:K12967]
8743  TNFSF10; TNF superfamily member 10 [KO:K04721]
8797  TNFRSF10A; TNF receptor superfamily member 10a [KO:K04722]
8795  TNFRSF10B; TNF receptor superfamily member 10b [KO:K04722]
356  FASLG; Fas ligand [KO:K04389]
355  FAS; Fas cell surface death receptor [KO:K04390]
7132  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
7416  VDAC1; voltage dependent anion channel 1 [KO:K05862]
54205  CYCS; cytochrome c, somatic [KO:K08738]
842  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
2932  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
3836  KPNA1; karyopherin subunit alpha 1 [KO:K15042]
3838  KPNA2; karyopherin subunit alpha 2 [KO:K15043]
7919  DDX39B; DExD-box helicase 39B [KO:K12812] [EC:3.6.4.13]
7514  XPO1; exportin 1 [KO:K14290]
3267  AGFG1; ArfGAP with FG repeats 1 [KO:K15044]
5578  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
5894  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
5604  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
91543  RSAD2; radical S-adenosyl methionine domain containing 2 [KO:K15045]
2224  FDPS; farnesyl diphosphate synthase [KO:K00787] [EC:2.5.1.10 2.5.1.1]
60  ACTB; actin beta [KO:K05692]
71  ACTG1; actin gamma 1 [KO:K05692]
10625  IVNS1ABP; influenza virus NS1A binding protein [KO:K15046]
10898  CPSF4; cleavage and polyadenylation specific factor 4 [KO:K14404]
8106  PABPN1; poly(A) binding protein nuclear 1 [KO:K14396]
390748  PABPN1L; poly(A) binding protein nuclear 1 like, cytoplasmic [KO:K14396]
100529063  BCL2L2-PABPN1; BCL2L2-PABPN1 readthrough [KO:K14396]
10482  NXF1; nuclear RNA export factor 1 [KO:K14284]
56001  NXF2; nuclear RNA export factor 2 [KO:K14284]
728343  NXF2B; nuclear RNA export factor 2B [KO:K14284]
55998  NXF5; nuclear RNA export factor 5 [KO:K14284]
56000  NXF3; nuclear RNA export factor 3 [KO:K14284]
29107  NXT1; nuclear transport factor 2 like export factor 1 [KO:K14285]
55916  NXT2; nuclear transport factor 2 like export factor 2 [KO:K14285]
8480  RAE1; ribonucleic acid export 1 [KO:K14298]
11100  HNRNPUL1; heterogeneous nuclear ribonucleoprotein U like 1 [KO:K15047]
4928  NUP98; nucleoporin 98 [KO:K14297]
5045  FURIN; furin, paired basic amino acid cleaving enzyme [KO:K01349] [EC:3.4.21.75]
84000  TMPRSS13; transmembrane serine protease 13 [KO:K09643]
5340  PLG; plasminogen [KO:K01315] [EC:3.4.21.7]
293  SLC25A6; solute carrier family 25 member 6 [KO:K05863]
5579  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
Compound
C00027  Hydrogen peroxide
C00080  H+
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
  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)
DOI:10.1016/j.micinf.2009.09.007
Reference
  Authors
Hale BG, Albrecht RA, Garcia-Sastre A
  Title
Innate immune evasion strategies of influenza viruses.
  Journal
Future Microbiol 5:23-41 (2010)
DOI:10.2217/fmb.09.108
Reference
  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)
DOI:10.1093/jac/dkp161
Reference
  Authors
von Itzstein M
  Title
The war against influenza: discovery and development of sialidase inhibitors.
  Journal
Nat Rev Drug Discov 6:967-74 (2007)
DOI:10.1038/nrd2400
Reference
  Authors
Garcia-Sastre A
  Title
Antiviral response in pandemic influenza viruses.
  Journal
Emerg Infect Dis 12:44-7 (2006)
DOI:10.3201/eid1201.051186
Reference
  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)
DOI:10.1586/14760584.7.9.1435
Reference
  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)
DOI:10.1016/j.it.2009.09.004
Reference
  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)
DOI:10.1016/j.biocel.2008.05.019
Reference
  Authors
Neumann G, Shinya K, Kawaoka Y
  Title
Molecular pathogenesis of H5N1 influenza virus infections.
  Journal
Antivir Ther 12:617-26 (2007)
Reference
  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)
DOI:10.1038/sj.icb.7100026
Reference
  Authors
Nayak DP, Balogun RA, Yamada H, Zhou ZH, Barman S
  Title
Influenza virus morphogenesis and budding.
  Journal
Virus Res 143:147-61 (2009)
DOI:10.1016/j.virusres.2009.05.010
Reference
  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)
DOI:10.1038/sj.onc.1209941
Reference
  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)
DOI:10.1111/j.1462-5822.2009.01309.x
Reference
  Authors
Pang IK, Iwasaki A
  Title
Inflammasomes as mediators of immunity against influenza virus.
  Journal
Trends Immunol 32:34-41 (2011)
DOI:10.1016/j.it.2010.11.004
Reference
  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)
DOI:10.1073/pnas.0610977104
Reference
  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)
DOI:10.1111/j.1462-5822.2006.00713.x
Reference
  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)
DOI:10.1038/nsmb847
Reference
  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)
DOI:10.1099/0022-1317-83-4-723
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
  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)
DOI:10.1002/rmv.657
KO pathway
ko05164   

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