KEGG   PATHWAY: lww05164
Entry
lww05164                    Pathway                                
Name
Influenza A - Leptonychotes weddellii (Weddell seal)
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
lww05164  Influenza A
lww05164

Organism
Leptonychotes weddellii (Weddell seal) [GN:lww]
Gene
102735356  tryptase-like isoform X2 [KO:K01340] [EC:3.4.21.59]
102744421  PLG; plasminogen isoform X2 [KO:K01315] [EC:3.4.21.7]
102741213  LOW QUALITY PROTEIN: cationic trypsin-like [KO:K01312] [EC:3.4.21.4]
102738811  PRSS2; trypsin-2 [KO:K01312] [EC:3.4.21.4]
102739415  cationic trypsin-like [KO:K01312] [EC:3.4.21.4]
102731356  transmembrane protease serine 2-like [KO:K09633] [EC:3.4.21.122]
102739626  TMPRSS4; transmembrane protease serine 4 isoform X1 [KO:K09635] [EC:3.4.21.-]
102731436  transmembrane protease serine 11D isoform X1 [KO:K09641] [EC:3.4.21.-]
102732903  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
102733293  OAS3; LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 3 [KO:K14216] [EC:2.7.7.84]
102731487  OAS2; LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 2 [KO:K14216] [EC:2.7.7.84]
102731794  OAS1; 2'-5'-oligoadenylate synthase 1 [KO:K14216] [EC:2.7.7.84]
102728083  RNASEL; LOW QUALITY PROTEIN: 2-5A-dependent ribonuclease [KO:K01165]
102741391  DNAJB1; dnaJ homolog subfamily B member 1 isoform X1 [KO:K09507]
102744420  DNAJC3; dnaJ homolog subfamily C member 3 [KO:K09523]
102731171  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase isoform X1 [KO:K16195] [EC:2.7.11.1]
102735186  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
102749328  TRIM25; E3 ubiquitin/ISG15 ligase TRIM25 [KO:K10652] [EC:2.3.2.27]
102746318  DDX58; probable ATP-dependent RNA helicase DDX58 [KO:K12646] [EC:5.6.2.6]
102744424  interferon-induced helicase C domain-containing protein 1 [KO:K12647] [EC:5.6.2.6]
102739816  NLRX1; NLR family member X1 isoform X1 [KO:K12653]
102727031  MAVS; LOW QUALITY PROTEIN: mitochondrial antiviral-signaling protein [KO:K12648]
102728853  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
102750184  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
102742694  IKBKG; NF-kappa-B essential modulator [KO:K07210]
102732489  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
102725682  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102732435  nuclear factor NF-kappa-B p105 subunit-like [KO:K02580]
102739707  RELA; transcription factor p65 [KO:K04735]
102737902  CALCOCO2; calcium-binding and coiled-coil domain-containing protein 2 [KO:K21348]
102725831  TLR3; toll-like receptor 3 isoform X1 [KO:K05401]
102737118  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
102749350  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
102748381  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
102732139  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
102747427  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
102749228  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
102749618  TLR4; toll-like receptor 4 [KO:K10160]
102744012  TLR7; toll-like receptor 7 [KO:K05404]
102737954  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
102741856  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
102737602  IRF7; interferon regulatory factor 7 isoform X3 [KO:K09447]
102740423  IL1A; interleukin-1 alpha isoform X1 [KO:K04383]
102739919  IL1B; interleukin-1 beta [KO:K04519]
102745902  IL6; interleukin-6 isoform X1 [KO:K05405]
102738603  IL12A; interleukin-12 subunit alpha [KO:K05406]
102740807  IL12B; interleukin-12 subunit beta [KO:K05425]
102743506  TNF; tumor necrosis factor [KO:K03156]
102737756  CXCL8; interleukin-8 [KO:K10030]
102740920  CCL5; C-C motif chemokine 5 [KO:K12499]
102740919  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
102747999  ICAM1; intercellular adhesion molecule 1 isoform X1 [KO:K06490]
102748540  LOW QUALITY PROTEIN: interferon alpha-14 [KO:K05414]
102747471  interferon alpha-1/2-like [KO:K05414]
102747757  interferon alpha-1/2-like [KO:K05414]
102750324  interferon alpha-2-like [KO:K05414]
102727550  interferon alpha-1/2-like [KO:K05414]
102749740  LOW QUALITY PROTEIN: interferon alpha-2-like [KO:K05414]
102748842  IFNB1; interferon beta [KO:K05415]
102734634  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
102750819  interferon alpha/beta receptor 2-like [KO:K05131]
102736730  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
102749508  non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
102740887  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
102731818  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
102739614  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
102750742  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
102734798  interferon-induced GTP-binding protein Mx1 [KO:K14754]
102735693  MX2; interferon-induced GTP-binding protein Mx2 [KO:K14754]
102729981  interferon-induced GTP-binding protein Mx2-like [KO:K14754]
102730286  interferon-induced GTP-binding protein Mx1-like [KO:K14754]
102742882  ADAR; double-stranded RNA-specific adenosine deaminase isoform X2 [KO:K12968] [EC:3.5.4.37]
102748183  PML; protein PML isoform X1 [KO:K10054] [EC:2.3.2.-]
102733689  IFNG; interferon gamma [KO:K04687]
102725692  IFNGR1; LOW QUALITY PROTEIN: interferon gamma receptor 1 [KO:K05132]
102748762  IFNGR2; interferon gamma receptor 2 [KO:K05133]
102745262  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
102750916  MHC class II transactivator isoform X1 [KO:K08060] [EC:2.7.11.1]
102733188  HLA class II histocompatibility antigen, DP alpha 1 chain-like isoform X1 [KO:K06752]
102748173  H-2 class II histocompatibility antigen, E-S beta chain-like [KO:K06752]
102747192  HLA class II histocompatibility antigen, DQ alpha 1 chain-like [KO:K06752]
102734456  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
102740784  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
102741082  DLA class II histocompatibility antigen, DR-1 beta chain isoform X1 [KO:K06752]
102747485  HLA class II histocompatibility antigen, DQ beta 2 chain isoform X1 [KO:K06752]
102748462  HLA class II histocompatibility antigen, DO beta chain isoform X2 [KO:K06752]
102750166  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
102750454  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
102725620  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800]
102727882  apoptosis-associated speck-like protein containing a CARD isoform X1 [KO:K12799]
102742078  IL18; interleukin-18 isoform X1 [KO:K05482]
102749969  IL33; interleukin-33 [KO:K12967]
102751021  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102726443  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102728383  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
102743753  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X4 [KO:K00922] [EC:2.7.1.153]
102749194  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102738988  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102747309  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102749871  AKT1; RAC-alpha serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
102734291  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102736121  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
102746891  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
102737670  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102744830  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
102738560  uncharacterized protein LOC102738560 isoform X1 [KO:K04722]
102745146  tumor necrosis factor ligand superfamily member 6-like [KO:K04389]
102738718  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
102739000  tumor necrosis factor receptor superfamily member 1A [KO:K03158]
102750365  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
102737084  FADD; FAS-associated death domain protein [KO:K02373]
102733039  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
115943885  BH3-interacting domain death agonist-like [KO:K04726]
102729504  apoptosis regulator BAX-like isoform X1 [KO:K02159]
102731986  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
102751218  voltage-dependent anion-selective channel protein 1-like [KO:K05862]
102734457  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
102734685  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
102750278  ADP/ATP translocase 3 [KO:K05863]
102737381  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
102745503  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
102725978  cytochrome c 2-like [KO:K08738]
102750923  cytochrome c [KO:K08738]
102726669  cytochrome c [KO:K08738]
102729908  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
102725545  caspase-9-like [KO:K04399] [EC:3.4.22.62]
102735000  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
102747483  LOW QUALITY PROTEIN: putative cleavage and polyadenylation specificity factor subunit 4-like protein [KO:K14404]
102726361  CPSF4; cleavage and polyadenylation specificity factor subunit 4 isoform X2 [KO:K14404]
102727505  PABPN1L; LOW QUALITY PROTEIN: embryonic polyadenylate-binding protein 2 [KO:K14396]
102746652  NXF1; nuclear RNA export factor 1 isoform X2 [KO:K14284]
102730566  nuclear RNA export factor 2 [KO:K14284]
102738211  NXT1; NTF2-related export protein 1 [KO:K14285]
102736471  NXT2; NTF2-related export protein 2 isoform X1 [KO:K14285]
102747238  heterogeneous nuclear ribonucleoprotein U-like protein 1 [KO:K15047]
102740161  RAE1; mRNA export factor [KO:K14298]
102739639  NUP98; nuclear pore complex protein Nup98-Nup96 [KO:K14297]
102748192  RSAD2; radical S-adenosyl methionine domain-containing protein 2 [KO:K15045]
102729337  FDPS; farnesyl pyrophosphate synthase isoform X2 [KO:K00787] [EC:2.5.1.1 2.5.1.10]
102726914  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102750302  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102745982  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102727849  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102730012  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102736013  ACTG1; actin, cytoplasmic 2 [KO:K05692]
102744309  ACTB; actin, cytoplasmic 1 [KO:K05692]
102737845  ras-related protein Rab-11A [KO:K07904]
102747064  RAB11B; ras-related protein Rab-11B [KO:K07905]
102729072  KPNA1; importin subunit alpha-5 [KO:K23940]
102728774  LOW QUALITY PROTEIN: importin subunit alpha-8-like [KO:K15043]
102747339  LOW QUALITY PROTEIN: importin subunit alpha-8-like [KO:K15043]
102750113  KPNA7; importin subunit alpha-8 [KO:K15043]
102730098  KPNA2; importin subunit alpha-1 [KO:K15043]
102733970  KPNA5; importin subunit alpha-6 isoform X1 [KO:K15042]
102725980  KPNA6; importin subunit alpha-7 isoform X1 [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
lww00900  Terpenoid backbone biosynthesis
lww03013  Nucleocytoplasmic transport
lww03015  mRNA surveillance pathway
lww04010  MAPK signaling pathway
lww04110  Cell cycle
lww04144  Endocytosis
lww04210  Apoptosis
lww04620  Toll-like receptor signaling pathway
lww04621  NOD-like receptor signaling pathway
lww04622  RIG-I-like receptor signaling pathway
lww04630  JAK-STAT signaling pathway
lww05416  Viral myocarditis
KO pathway
ko05164   
LinkDB

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