KEGG   PATHWAY: pcad05164
Entry
pcad05164                   Pathway                                
Name
Influenza A - Physeter catodon (sperm whale)
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
pcad05164  Influenza A
pcad05164

Organism
Physeter catodon (sperm whale) [GN:pcad]
Gene
102979031  plasminogen isoform X1 [KO:K01315] [EC:3.4.21.7]
102983302  trypsin-like isoform X1 [KO:K01312] [EC:3.4.21.4]
102982385  TMPRSS2; transmembrane protease serine 2 [KO:K09633] [EC:3.4.21.122]
102975998  TMPRSS4; transmembrane protease serine 4 isoform X1 [KO:K09635] [EC:3.4.21.-]
102994577  TMPRSS11D; transmembrane protease serine 11D [KO:K09641] [EC:3.4.21.-]
102974383  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
102995339  OAS2; 2'-5'-oligoadenylate synthase 2 isoform X1 [KO:K14216] [EC:2.7.7.84]
102995791  OAS1; 2'-5'-oligoadenylate synthase 1 isoform X1 [KO:K14216] [EC:2.7.7.84]
102996067  2'-5'-oligoadenylate synthase 1-like [KO:K14216] [EC:2.7.7.84]
102982973  RNASEL; 2-5A-dependent ribonuclease isoform X1 [KO:K01165]
102976232  DNAJB1; dnaJ homolog subfamily B member 1 [KO:K09507]
102986724  DNAJC3; dnaJ homolog subfamily C member 3 isoform X1 [KO:K09523]
102977777  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
102975968  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
102991542  TRIM25; E3 ubiquitin/ISG15 ligase TRIM25 isoform X1 [KO:K10652] [EC:2.3.2.27]
102977378  RIGI; LOW QUALITY PROTEIN: antiviral innate immune response receptor RIG-I [KO:K12646] [EC:5.6.2.6]
102994692  IFIH1; interferon-induced helicase C domain-containing protein 1 [KO:K12647] [EC:5.6.2.6]
102992829  NLRX1; NLR family member X1 isoform X1 [KO:K12653]
102978512  AP5S1; AP-5 complex subunit sigma-1 isoform X2 [KO:K12648]
102977668  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X2 [KO:K04467] [EC:2.7.11.10]
102976706  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
114485485  NF-kappa-B essential modulator-like isoform X1 [KO:K07210]
102980964  IKBKG; NF-kappa-B essential modulator [KO:K07210]
102995931  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
102973672  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102981135  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102974198  RELA; transcription factor p65 isoform X1 [KO:K04735]
102982505  CALCOCO2; calcium-binding and coiled-coil domain-containing protein 2 [KO:K21348]
102990625  LOW QUALITY PROTEIN: toll-like receptor 3 [KO:K05401]
102975837  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
102974816  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
102994775  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
102994478  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
102986279  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
114485354  CREB-binding protein [KO:K04498] [EC:2.3.1.48]
102983478  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
102991594  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
102983076  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
102990770  TLR7; toll-like receptor 7 isoform X1 [KO:K05404]
102974002  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
102982312  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
102996452  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
102993910  IL1A; interleukin-1 alpha [KO:K04383]
102994188  IL1B; interleukin-1 beta [KO:K04519]
102980126  IL6; interleukin-6 [KO:K05405]
102982335  IL12A; interleukin-12 subunit alpha [KO:K05406]
102980587  IL12B; interleukin-12 subunit beta [KO:K05425]
102983069  TNF; tumor necrosis factor [KO:K03156]
102979960  CXCL8; interleukin-8 [KO:K10030]
102990067  monocyte chemotactic protein 1B [KO:K14624]
102975625  CCL5; C-C motif chemokine 5 [KO:K12499]
102993287  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
102988478  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
112065747  interferon alpha-1-like [KO:K05414]
102980314  interferon alpha-1-like [KO:K05414]
102990155  IFNB1; interferon beta [KO:K05415]
102991034  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
102989482  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
102988182  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
102985137  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
102978137  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
102977655  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
102981574  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
102992486  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
102982101  LOW QUALITY PROTEIN: interferon-induced GTP-binding protein Mx1 [KO:K14754]
102979811  ADAR; double-stranded RNA-specific adenosine deaminase isoform X1 [KO:K12968] [EC:3.5.4.37]
102983450  PML; protein PML isoform X1 [KO:K10054] [EC:2.3.2.-]
102981551  IFNG; interferon gamma [KO:K04687]
102977921  IFNGR1; interferon gamma receptor 1 [KO:K05132]
102997040  IFNGR2; interferon gamma receptor 2 isoform X2 [KO:K05133]
102978811  JAK2; tyrosine-protein kinase JAK2 isoform X2 [KO:K04447] [EC:2.7.10.2]
102993456  CIITA; MHC class II transactivator isoform X1 [KO:K08060] [EC:2.7.11.1]
102994322  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
102973944  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
102976012  HLA class II histocompatibility antigen, DQ beta 1 chain isoform X2 [KO:K06752]
102973764  DLA class II histocompatibility antigen, DR-1 beta chain-like isoform X1 [KO:K06752]
102976287  HLA class II histocompatibility antigen, DQ alpha 2 chain isoform X2 [KO:K06752]
102992942  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
102974479  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
102994605  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
102978546  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
102976103  NLRP3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800]
102986634  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
102995954  LOW QUALITY PROTEIN: apoptosis-associated speck-like protein containing a CARD [KO:K12799]
102982110  CASP1; caspase-1 [KO:K01370] [EC:3.4.22.36]
102976313  IL18; interleukin-18 [KO:K05482]
102989473  IL33; interleukin-33 [KO:K12967]
102975555  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102991779  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102991192  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
102986098  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102978952  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102977108  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102981524  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102976971  AKT3; RAC-gamma serine/threonine-protein kinase isoform X3 [KO:K04456] [EC:2.7.11.1]
102990087  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102987349  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
102985179  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
102992532  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
102992913  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
102979472  tumor necrosis factor receptor superfamily member 10B [KO:K04722]
102980036  tumor necrosis factor receptor superfamily member 10B isoform X1 [KO:K04722]
102979864  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
102985097  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
102980613  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
102986061  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
102973514  FAS-associated death domain protein isoform X1 [KO:K02373]
112067437  FAS-associated death domain protein isoform X1 [KO:K02373]
102988082  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
102991092  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
102991951  VDAC1; voltage-dependent anion-selective channel protein 1 isoform X2 [KO:K05862]
102974857  LOW QUALITY PROTEIN: voltage-dependent anion-selective channel protein 1-like [KO:K05862]
102992414  voltage-dependent anion-selective channel protein 1-like [KO:K05862]
102978018  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
102975203  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
102985148  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
102990817  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
102996437  LOW QUALITY PROTEIN: uncharacterized protein LOC102996437 [KO:K05863]
102980282  cytochrome c-like [KO:K08738]
112066660  cytochrome c [KO:K08738]
112063874  cytochrome c-like [KO:K08738]
102978471  cytochrome c-like [KO:K08738]
102986675  cytochrome c-like [KO:K08738]
102977457  cytochrome c 2 [KO:K08738]
102978194  cytochrome c-like [KO:K08738]
102994125  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
102989458  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
102977692  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
102995601  CPSF4L; putative cleavage and polyadenylation specificity factor subunit 4-like protein [KO:K14404]
102996937  CPSF4; cleavage and polyadenylation specificity factor subunit 4 isoform X2 [KO:K14404]
102995347  embryonic polyadenylate-binding protein 2 isoform X1 [KO:K14396]
102977911  NXF1; nuclear RNA export factor 1 [KO:K14284]
102977204  nuclear RNA export factor 2 [KO:K14284]
114484661  LOW QUALITY PROTEIN: nuclear RNA export factor 2-like [KO:K14284]
102973772  LOW QUALITY PROTEIN: nuclear RNA export factor 3-like [KO:K14284]
102986802  nuclear RNA export factor 3-like [KO:K14284]
102994592  LOW QUALITY PROTEIN: nuclear RNA export factor 2-like [KO:K14284]
112066110  NTF2-related export protein 2-like [KO:K14285]
102976925  NTF2-related export protein 2-like [KO:K14285]
102996136  NXT1; NTF2-related export protein 1 [KO:K14285]
102978168  NTF2-related export protein 2 [KO:K14285]
102980262  heterogeneous nuclear ribonucleoprotein U-like protein 1 isoform X1 [KO:K15047]
114483948  HNRNPUL1; heterogeneous nuclear ribonucleoprotein U-like protein 1 [KO:K15047]
102991445  mRNA export factor RAE1 [KO:K14298]
102992241  nuclear pore complex protein Nup98-Nup96 isoform X1 [KO:K14297]
114485016  nuclear pore complex protein Nup98-Nup96 [KO:K14297]
102974487  RSAD2; S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 [KO:K15045]
102980744  FDPS; farnesyl pyrophosphate synthase isoform X1 [KO:K00787] [EC:2.5.1.1 2.5.1.10]
102974888  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
102987866  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
102992191  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102994150  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102984305  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102989074  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102988048  ACTG1; actin, cytoplasmic 2 [KO:K05692]
102988905  actin, cytoplasmic 1 [KO:K05692]
112063645  actin, cytoplasmic 1 isoform X2 [KO:K05692]
102978590  RAB11A; ras-related protein Rab-11A isoform X2 [KO:K07904]
102993498  RAB11B; ras-related protein Rab-11B [KO:K07905]
102982682  XPO1; exportin-1 [KO:K14290]
102991965  KPNA1; importin subunit alpha-5 [KO:K23940]
102976045  KPNA7; importin subunit alpha-8 isoform X4 [KO:K15043]
102983234  KPNA2; importin subunit alpha-1 [KO:K15043]
112062043  LOW QUALITY PROTEIN: importin subunit alpha-8-like [KO:K15043]
102978516  LOW QUALITY PROTEIN: importin subunit alpha-1-like [KO:K15043]
102979876  LOW QUALITY PROTEIN: importin subunit alpha-1-like [KO:K15043]
102983770  LOW QUALITY PROTEIN: importin subunit alpha-1-like [KO:K15043]
102975984  KPNA5; importin subunit alpha-6 [KO:K15042]
102994970  KPNA6; importin subunit alpha-7 isoform X2 [KO:K15042]
Compound
C00027  Hydrogen peroxide
C00080  H+
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:24225499
  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
PMID:19565019
  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
PMID:27751627
  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
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)
DOI:10.1016/j.biocel.2008.05.019
Reference
PMID:23977434
  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
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)
DOI:10.2217/fmb.09.108
Reference
PMID:21698289
  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
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)
DOI:10.1016/j.micinf.2009.09.007
Reference
PMID:23170167
  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
PMID:30487536
  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
PMID:29556226
  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
PMID:20130137
  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
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)
DOI:10.1586/14760584.7.9.1435
Reference
PMID:27231932
  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
PMID:30510918
  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
PMID:21971186
  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
PMID:30254192
  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
PMID:30545063
  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
PMID:21253874
  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
PMID:26008706
  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
PMID:30079062
  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
PMID:23236273
  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
pcad00900  Terpenoid backbone biosynthesis
pcad03013  Nucleocytoplasmic transport
pcad03015  mRNA surveillance pathway
pcad04010  MAPK signaling pathway
pcad04110  Cell cycle
pcad04144  Endocytosis
pcad04210  Apoptosis
pcad04620  Toll-like receptor signaling pathway
pcad04621  NOD-like receptor signaling pathway
pcad04622  RIG-I-like receptor signaling pathway
pcad04630  JAK-STAT signaling pathway
pcad05416  Viral myocarditis
KO pathway
ko05164   
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