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
Influenza A
hsa05164

All organismsOrtholog table
Disease
H00398  
Influenza
H00399  
Avian influenza
Organism
Homo sapiens (human) [GN:hsa]
Gene
5646  
PRSS3; protease, serine 3 [KO:K01312] [EC:3.4.21.4]
5645  
PRSS2; protease, serine 2 [KO:K01312] [EC:3.4.21.4]
5644  
PRSS1; protease, serine 1 [KO:K01312] [EC:3.4.21.4]
7113  
TMPRSS2; transmembrane protease, serine 2 [KO:K09633] [EC:3.4.21.-]
56649  
TMPRSS4; transmembrane protease, serine 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; myeloid differentiation primary response 88 [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]
8794  
TNFRSF10C; TNF receptor superfamily member 10c [KO:K04722]
8793  
TNFRSF10D; TNF receptor superfamily member 10d [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]
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 protease, serine 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
 

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