KEGG   PATHWAY: sara05164
Entry
sara05164                   Pathway                                
Name
Influenza A - Sorex araneus (European shrew)
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
sara05164  Influenza A
sara05164

Organism
Sorex araneus (European shrew) [GN:sara]
Gene
101547756  tryptase-like isoform X1 [KO:K01340] [EC:3.4.21.59]
101557844  PLG; plasminogen [KO:K01315] [EC:3.4.21.7]
101548309  anionic trypsin-like [KO:K01312] [EC:3.4.21.4]
101548575  anionic trypsin-like [KO:K01312] [EC:3.4.21.4]
101548835  anionic trypsin [KO:K01312] [EC:3.4.21.4]
101549099  trypsin [KO:K01312] [EC:3.4.21.4]
105942995  anionic trypsin [KO:K01312] [EC:3.4.21.4]
101547383  TMPRSS2; transmembrane protease serine 2 [KO:K09633] [EC:3.4.21.122]
101544593  TMPRSS4; transmembrane protease serine 4 [KO:K09635] [EC:3.4.21.-]
101547541  TMPRSS11D; transmembrane protease serine 11D [KO:K09641] [EC:3.4.21.-]
101547658  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
101552816  2'-5'-oligoadenylate synthase 3 [KO:K14216] [EC:2.7.7.84]
101549296  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
101557552  DNAJB1; dnaJ homolog subfamily B member 1 [KO:K09507]
101539879  DNAJC3; dnaJ homolog subfamily C member 3 [KO:K09523]
101542873  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
101555179  eukaryotic translation initiation factor 2 subunit 1-like [KO:K03237]
101552557  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
101556886  TRIM25; E3 ubiquitin/ISG15 ligase TRIM25 [KO:K10652] [EC:2.3.2.27]
101557300  DDX58; LOW QUALITY PROTEIN: probable ATP-dependent RNA helicase DDX58 [KO:K12646] [EC:5.6.2.6]
101559134  IFIH1; interferon-induced helicase C domain-containing protein 1 [KO:K12647] [EC:5.6.2.6]
101552797  NLRX1; NLR family member X1 [KO:K12653]
101542406  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
101538389  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
101540472  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
101536840  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
101550362  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
101556810  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101549580  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
101543163  RELA; transcription factor p65 [KO:K04735]
101553423  CALCOCO2; LOW QUALITY PROTEIN: calcium-binding and coiled-coil domain-containing protein 2 [KO:K21348]
101552190  TLR3; toll-like receptor 3 [KO:K05401]
101557102  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
101538970  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
101542553  TBK1; serine/threonine-protein kinase TBK1 isoform X2 [KO:K05410] [EC:2.7.11.10]
101552901  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
101542890  IRF3; interferon regulatory factor 3 [KO:K05411]
101542504  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
101558222  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
101548691  TLR4; toll-like receptor 4 [KO:K10160]
101555293  TLR7; toll-like receptor 7 [KO:K05404]
101547526  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
101545292  IRF7; interferon regulatory factor 7 [KO:K09447]
101548664  IL1A; interleukin-1 alpha [KO:K04383]
101550075  IL1B; interleukin-1 beta [KO:K04519]
101540363  IL6; interleukin-6 [KO:K05405]
101539403  IL12A; interleukin-12 subunit alpha [KO:K05406]
101542768  IL12B; interleukin-12 subunit beta [KO:K05425]
101558664  TNF; tumor necrosis factor [KO:K03156]
101559441  CXCL8; interleukin-8 [KO:K10030]
101545218  C-C motif chemokine 2-like [KO:K14624]
101542043  C-C motif chemokine 2-like [KO:K14624]
101548921  CCL5; C-C motif chemokine 5 [KO:K12499]
101542348  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
101549044  ICAM1; LOW QUALITY PROTEIN: intercellular adhesion molecule 1 [KO:K06490]
101549593  LOW QUALITY PROTEIN: interferon alpha-14 [KO:K05414]
101548268  IFNB1; interferon beta [KO:K05415]
101558656  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
101559190  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
101556525  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
101550098  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
101555243  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
101554357  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
101550386  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
101556712  IRF9; interferon regulatory factor 9 [KO:K04693]
101547648  MX1; interferon-induced GTP-binding protein Mx1 [KO:K14754]
101547923  MX2; interferon-induced GTP-binding protein Mx2 [KO:K14754]
101553112  ADAR; double-stranded RNA-specific adenosine deaminase isoform X1 [KO:K12968] [EC:3.5.4.37]
101549024  PML; protein PML [KO:K10054] [EC:2.3.2.-]
101540972  IFNG; interferon gamma [KO:K04687]
101546718  IFNGR1; interferon gamma receptor 1 [KO:K05132]
101558386  IFNGR2; interferon gamma receptor 2 [KO:K05133]
101550196  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
101543552  CIITA; MHC class II transactivator [KO:K08060] [EC:2.7.11.1]
101559440  HLA class II histocompatibility antigen, DQ beta 2 chain-like [KO:K06752]
101537059  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
101537584  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
101537862  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
101538134  HLA class II histocompatibility antigen, DQ beta 2 chain-like [KO:K06752]
101538664  SLA class II histocompatibility antigen, DQ haplotype C beta chain-like [KO:K06752]
101538932  LOW QUALITY PROTEIN: rano class II histocompatibility antigen, A beta chain-like [KO:K06752]
101539716  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
101540766  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
101544551  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like isoform X1 [KO:K06752]
101544821  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like isoform X1 [KO:K06752]
101557827  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
101558101  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
101558910  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
101539188  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
101540504  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
101546398  PYCARD; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
101552446  caspase-1-like [KO:K01370] [EC:3.4.22.36]
101559035  IL18; interleukin-18 [KO:K05482]
101540596  IL33; interleukin-33 [KO:K12967]
101547106  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101541868  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101540938  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101542917  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101556597  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101548304  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101543096  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101559009  AKT2; RAC-beta serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101543371  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101541507  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
101559274  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
101556590  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
101536897  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
101537204  TNFRSF10B; tumor necrosis factor receptor superfamily member 10B [KO:K04722]
101541261  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
101557571  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
101537769  FADD; FAS-associated death domain protein [KO:K02373]
101543078  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
101546492  BID; BH3-interacting domain death agonist [KO:K04726]
101540951  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
101538133  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
101557440  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
101553449  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
101538265  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
101554026  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
101543714  ADP/ATP translocase 3 [KO:K05863]
101558408  cytochrome c, somatic [KO:K08738]
101538879  cytochrome c-like [KO:K08738]
101549686  cytochrome c, somatic [KO:K08738]
101543860  cytochrome c 2 [KO:K08738]
101537432  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
101537803  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
101539340  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
101541547  CPSF4; cleavage and polyadenylation specificity factor subunit 4 isoform X1 [KO:K14404]
101547318  polyadenylate-binding protein 2 [KO:K14396]
101538486  PABPN1L; embryonic polyadenylate-binding protein 2 [KO:K14396]
101544098  embryonic polyadenylate-binding protein 2-like [KO:K14396]
101537846  nuclear RNA export factor 2 [KO:K14284]
101540443  NXF1; nuclear RNA export factor 1 isoform X1 [KO:K14284]
101554047  nuclear RNA export factor 2-like [KO:K14284]
101538019  NXT1; NTF2-related export protein 1 [KO:K14285]
101539503  NXT2; NTF2-related export protein 2 [KO:K14285]
101551616  HNRNPUL1; heterogeneous nuclear ribonucleoprotein U-like protein 1 isoform X1 [KO:K15047]
101538147  RAE1; mRNA export factor [KO:K14298]
101548259  nuclear pore complex protein Nup98-Nup96 isoform X1 [KO:K14297]
101543385  RSAD2; radical S-adenosyl methionine domain-containing protein 2 [KO:K15045]
101558646  FDPS; farnesyl pyrophosphate synthase [KO:K00787] [EC:2.5.1.1 2.5.1.10]
101551961  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
101545329  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101550720  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101555057  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101559341  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
101541587  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
101545848  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
101545833  actin, cytoplasmic 2-like [KO:K05692]
101557116  ACTG1; actin, cytoplasmic 2 [KO:K05692]
101548998  actin-5C-like [KO:K05692]
101544993  ACTB; actin, cytoplasmic 1 isoform X1 [KO:K05692]
101550461  RAB11A; ras-related protein Rab-11A [KO:K07904]
101552830  RAB11B; ras-related protein Rab-11B [KO:K07905]
101557251  XPO1; exportin-1 [KO:K14290]
101553595  KPNA1; importin subunit alpha-5 [KO:K23940]
101553897  KPNA7; importin subunit alpha-8 [KO:K15043]
101552493  KPNA2; importin subunit alpha-1 [KO:K15043]
101550348  KPNA5; importin subunit alpha-6 [KO:K15042]
101553585  KPNA6; importin subunit alpha-7 isoform X1 [KO:K15042]
101541678  LOW QUALITY PROTEIN: importin subunit alpha-7-like [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
sara00900  Terpenoid backbone biosynthesis
sara03013  Nucleocytoplasmic transport
sara03015  mRNA surveillance pathway
sara04010  MAPK signaling pathway
sara04110  Cell cycle
sara04144  Endocytosis
sara04210  Apoptosis
sara04620  Toll-like receptor signaling pathway
sara04621  NOD-like receptor signaling pathway
sara04622  RIG-I-like receptor signaling pathway
sara04630  JAK-STAT signaling pathway
sara05416  Viral myocarditis
KO pathway
ko05164   
LinkDB

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