KEGG   PATHWAY: hsa05164
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 and IRF3. 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 disease: viral
Pathway map
hsa05164  Influenza A
hsa05164

Network
nt06110  MAPK signaling (viruses and bacteria)
nt06114  PI3K signaling (viruses)
nt06122  IFN signaling (viruses)
nt06130  Cell cycle (viruses)
nt06131  Apoptosis (viruses and bacteria)
nt06133  RLR signaling (viruses)
nt06137  OAS/RNase L pathway (viruses)
nt06138  PKR-eIF2alpha signaling (viruses)
nt06139  NLR signaling (viruses and bacteria)
nt06170  Influenza A virus (IAV)
  Element
N00724  IAV NS1 to oligoadenylate synthetase (OAS)/RNase L pathway
N00725  IAV NS1 to PKR-eIF2alpha signaling pathway
N00726  IAV NP to PKR-eIF2alpha signaling pathway
N00727  IAV NS1 to RIG-I-like receptor signaling pathway
N00728  IAV NS1 to RIG-I-like receptor signaling pathway
N00729  IAV NS1 to RIG-I-like receptor signaling pathway
N00730  IAV NS1 to RIG-I-like receptor signaling pathway
N00732  IAV PB1-F2/PB2 to RIG-I-like receptor signaling pathway
N00734  IAV PB1-F2/PB2 to RIG-I-like receptor signaling pathway
N00736  IAV NS1 to PI3K signaling pathway
N00738  IAV NS1 to IFN signaling pathway
N00741  IAV M2 to cell cycle G1/S
N00743  IAV NS1 to NLRP3 inflammasome signaling pathway
N00744  IAV HA to ERK signaling pathway
N00745  IAV PB1-F2 to intrinsic apoptotic pathway
N00746  IAV NS1 to nuclear export of mRNA
Disease
H00398  Influenza
H00399  Avian influenza
Organism
Homo sapiens (human) [GN:hsa]
Gene
23430  TPSD1; tryptase delta 1 [KO:K01340] [EC:3.4.21.59]
7177  TPSAB1; tryptase alpha/beta 1 [KO:K01340] [EC:3.4.21.59]
64499  TPSB2; tryptase beta 2 [KO:K01340] [EC:3.4.21.59]
5340  PLG; plasminogen [KO:K01315] [EC:3.4.21.7]
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.-]
9407  TMPRSS11D; transmembrane serine protease 11D [KO:K09641] [EC:3.4.21.-]
5579  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
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]
5610  EIF2AK2; eukaryotic translation initiation factor 2 alpha kinase 2 [KO:K16195] [EC:2.7.11.1]
1965  EIF2S1; eukaryotic translation initiation factor 2 subunit alpha [KO:K03237]
7706  TRIM25; tripartite motif containing 25 [KO:K10652] [EC:2.3.2.27]
23586  DDX58; DExD/H-box helicase 58 [KO:K12646] [EC:3.6.4.13]
64135  IFIH1; interferon induced with helicase C domain 1 [KO:K12647] [EC:3.6.4.13]
79671  NLRX1; NLR family member X1 [KO:K12653]
57506  MAVS; mitochondrial antiviral signaling protein [KO:K12648]
1147  CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:2.7.11.10]
3551  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
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]
10241  CALCOCO2; calcium binding and coiled-coil domain 2 [KO:K21348]
7098  TLR3; toll like receptor 3 [KO:K05401]
148022  TICAM1; toll like receptor adaptor molecule 1 [KO:K05842]
7187  TRAF3; TNF receptor associated factor 3 [KO:K03174]
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]
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]
9021  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
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]
4599  MX1; MX dynamin like GTPase 1 [KO:K14754]
4600  MX2; MX dynamin like GTPase 2 [KO:K14754]
103  ADAR; adenosine deaminase RNA specific [KO:K12968] [EC:3.5.4.37]
5371  PML; PML nuclear body scaffold [KO:K10054] [EC:2.3.2.-]
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] [EC:2.7.11.1]
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]
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]
896  CCND3; cyclin D3 [KO:K10152]
1019  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
1021  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
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]
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:3.4.22.61]
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]
7416  VDAC1; voltage dependent anion channel 1 [KO:K05862]
291  SLC25A4; solute carrier family 25 member 4 [KO:K05863]
292  SLC25A5; solute carrier family 25 member 5 [KO:K05863]
293  SLC25A6; solute carrier family 25 member 6 [KO:K05863]
83447  SLC25A31; solute carrier family 25 member 31 [KO:K05863]
54205  CYCS; cytochrome c, somatic [KO:K08738]
317  APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
842  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
836  CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
10898  CPSF4; cleavage and polyadenylation specific factor 4 [KO:K14404]
642843  CPSF4L; cleavage and polyadenylation specific factor 4 like [KO:K14404]
8106  PABPN1; poly(A) binding protein nuclear 1 [KO:K14396]
390748  PABPN1L; PABPN1 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]
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]
11100  HNRNPUL1; heterogeneous nuclear ribonucleoprotein U like 1 [KO:K15047]
8480  RAE1; ribonucleic acid export 1 [KO:K14298]
4928  NUP98; nucleoporin 98 and 96 precursor [KO:K14297]
91543  RSAD2; radical S-adenosyl methionine domain containing 2 [KO:K15045]
2224  FDPS; farnesyl diphosphate synthase [KO:K00787] [EC:2.5.1.1 2.5.1.10]
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]
71  ACTG1; actin gamma 1 [KO:K05692]
60  ACTB; actin beta [KO:K05692]
8766  RAB11A; RAB11A, member RAS oncogene family [KO:K07904]
9230  RAB11B; RAB11B, member RAS oncogene family [KO:K07905]
7514  XPO1; exportin 1 [KO:K14290]
3836  KPNA1; karyopherin subunit alpha 1 [KO:K23940]
3838  KPNA2; karyopherin subunit alpha 2 [KO:K15043]
402569  KPNA7; karyopherin subunit alpha 7 [KO:K15043]
23633  KPNA6; karyopherin subunit alpha 6 [KO:K15042]
3841  KPNA5; karyopherin subunit alpha 5 [KO:K15042]
Compound
C00027  Hydrogen peroxide
C00080  H+
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
Edinger TO, Pohl MO, Stertz S
  Title
Entry of influenza A virus: host factors and antiviral targets.
  Journal
J Gen Virol 95:263-77 (2014)
DOI:10.1099/vir.0.059477-0
Reference
  Authors
Kido H, Okumura Y, Takahashi E, Pan HY, Wang S, Chida J, Le TQ, Yano M
  Title
Host envelope glycoprotein processing proteases are indispensable for entry into human cells by seasonal and highly pathogenic avian influenza viruses.
  Journal
J Mol Genet Med 3:167-75 (2008)
Reference
  Authors
Ramakrishnan B, Viswanathan K, Tharakaraman K, Dancik V, Raman R, Babcock GJ, Shriver Z, Sasisekharan R
  Title
A Structural and Mathematical Modeling Analysis of the Likelihood of Antibody-Dependent Enhancement in Influenza.
  Journal
Trends Microbiol 24:933-943 (2016)
DOI:10.1016/j.tim.2016.09.003
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
Michael P, Brabant D, Bleiblo F, Ramana CV, Rutherford M, Khurana S, Tai TC, Kumar A, Kumar A
  Title
Influenza A induced cellular signal transduction pathways.
  Journal
J Thorac Dis 5 Suppl 2:S132-41 (2013)
DOI:10.3978/j.issn.2072-1439.2013.07.42
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
Sharma K, Tripathi S, Ranjan P, Kumar P, Garten R, Deyde V, Katz JM, Cox NJ, Lal RB, Sambhara S, Lal SK
  Title
Influenza A virus nucleoprotein exploits Hsp40 to inhibit PKR activation.
  Journal
PLoS One 6:e20215 (2011)
DOI:10.1371/journal.pone.0020215
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
van de Sandt CE, Kreijtz JH, Rimmelzwaan GF
  Title
Evasion of influenza A viruses from innate and adaptive immune responses.
  Journal
Viruses 4:1438-76 (2012)
DOI:10.3390/v4091438
Reference
  Authors
Long JS, Mistry B, Haslam SM, Barclay WS
  Title
Host and viral determinants of influenza A virus species specificity.
  Journal
Nat Rev Microbiol 17:67-81 (2019)
DOI:10.1038/s41579-018-0115-z
Reference
  Authors
Chen X, Liu S, Goraya MU, Maarouf M, Huang S, Chen JL
  Title
Host Immune Response to Influenza A Virus Infection.
  Journal
Front Immunol 9:320 (2018)
DOI:10.3389/fimmu.2018.00320
Reference
  Authors
Lu X, Masic A, Li Y, Shin Y, Liu Q, Zhou Y
  Title
The PI3K/Akt pathway inhibits influenza A virus-induced Bax-mediated apoptosis by negatively regulating the JNK pathway via ASK1.
  Journal
J Gen Virol 91:1439-49 (2010)
DOI:10.1099/vir.0.018465-0
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
Le Sage V, Cinti A, Amorim R, Mouland AJ
  Title
Adapting the Stress Response: Viral Subversion of the mTOR Signaling Pathway.
  Journal
Viruses 8:E152 (2016)
DOI:10.3390/v8060152
Reference
  Authors
Fan Y, Sanyal S, Bruzzone R
  Title
Breaking Bad: How Viruses Subvert the Cell Cycle.
  Journal
Front Cell Infect Microbiol 8:396 (2018)
DOI:10.3389/fcimb.2018.00396
Reference
  Authors
Varga ZT, Palese P
  Title
The influenza A virus protein PB1-F2: killing two birds with one stone?
  Journal
Virulence 2:542-6 (2011)
DOI:10.4161/viru.2.6.17812
Reference
  Authors
Atkin-Smith GK, Duan M, Chen W, Poon IKH
  Title
The induction and consequences of Influenza A virus-induced cell death.
  Journal
Cell Death Dis 9:1002 (2018)
DOI:10.1038/s41419-018-1035-6
Reference
  Authors
Nogales A, Martinez-Sobrido L, Topham DJ, DeDiego ML
  Title
Modulation of Innate Immune Responses by the Influenza A NS1 and PA-X Proteins.
  Journal
Viruses 10:E708 (2018)
DOI:10.3390/v10120708
Reference
  Authors
Dai X, Zhang L, Hong T
  Title
Host cellular signaling induced by influenza virus.
  Journal
Sci China Life Sci 54:68-74 (2011)
DOI:10.1007/s11427-010-4116-z
Reference
  Authors
Li J, Yu M, Zheng W, Liu W
  Title
Nucleocytoplasmic shuttling of influenza A virus proteins.
  Journal
Viruses 7:2668-82 (2015)
DOI:10.3390/v7052668
Reference
  Authors
Dou D, Revol R, Ostbye H, Wang H, Daniels R
  Title
Influenza A Virus Cell Entry, Replication, Virion Assembly and Movement.
  Journal
Front Immunol 9:1581 (2018)
DOI:10.3389/fimmu.2018.01581
Reference
  Authors
Paterson D, Fodor E
  Title
Emerging roles for the influenza A virus nuclear export protein (NEP).
  Journal
PLoS Pathog 8:e1003019 (2012)
DOI:10.1371/journal.ppat.1003019
Related
pathway
hsa00900  Terpenoid backbone biosynthesis
hsa03013  Nucleocytoplasmic transport
hsa03015  mRNA surveillance pathway
hsa04010  MAPK signaling pathway
hsa04110  Cell cycle
hsa04144  Endocytosis
hsa04210  Apoptosis
hsa04620  Toll-like receptor signaling pathway
hsa04621  NOD-like receptor signaling pathway
hsa04622  RIG-I-like receptor signaling pathway
hsa04630  JAK-STAT signaling pathway
hsa05416  Viral myocarditis
KO pathway
ko05164   
LinkDB

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