KEGG   PATHWAY: pale05164
Entry
pale05164                   Pathway                                
Name
Influenza A - Pteropus alecto (black flying fox)
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
pale05164  Influenza A
pale05164

Organism
Pteropus alecto (black flying fox) [GN:pale]
Gene
102890577  TPSB2; tryptase beta-2 [KO:K01340] [EC:3.4.21.59]
102888257  PLG; plasminogen [KO:K01315] [EC:3.4.21.7]
102897268  anionic trypsin [KO:K01312] [EC:3.4.21.4]
102884423  TMPRSS2; transmembrane protease serine 2 [KO:K09633] [EC:3.4.21.122]
102890324  TMPRSS4; transmembrane protease serine 4 [KO:K09635] [EC:3.4.21.-]
102884252  TMPRSS11D; transmembrane protease serine 11D [KO:K09641] [EC:3.4.21.-]
102880663  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
102879074  OAS1; 2'-5'-oligoadenylate synthase 1 [KO:K14216] [EC:2.7.7.84]
102879322  OAS3; 2'-5'-oligoadenylate synthase 3 isoform X1 [KO:K14216] [EC:2.7.7.84]
102889470  OAS2; LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 2 [KO:K14216] [EC:2.7.7.84]
102894053  RNASEL; 2-5A-dependent ribonuclease isoform X1 [KO:K01165]
102888110  DNAJB1; dnaJ homolog subfamily B member 1 [KO:K09507]
102885436  DNAJC3; dnaJ homolog subfamily C member 3 isoform X2 [KO:K09523]
102890643  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
102884507  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
102879209  TRIM25; E3 ubiquitin/ISG15 ligase TRIM25 [KO:K10652] [EC:2.3.2.27]
102881037  DDX58; probable ATP-dependent RNA helicase DDX58 [KO:K12646] [EC:5.6.2.6]
102888688  IFIH1; interferon-induced helicase C domain-containing protein 1 [KO:K12647] [EC:5.6.2.6]
102894899  NLRX1; NLR family member X1 isoform X1 [KO:K12653]
102892463  MAVS; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
102879469  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
102893261  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
102880203  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
102881802  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
102891056  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102880692  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102878395  RELA; transcription factor p65 [KO:K04735]
102879552  CALCOCO2; calcium-binding and coiled-coil domain-containing protein 2 isoform X1 [KO:K21348]
102882731  TLR3; toll-like receptor 3 precursor [KO:K05401]
102896235  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
102881091  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
102878859  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
102889768  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
102878862  IRF3; interferon regulatory factor 3 isoform X2 [KO:K05411]
102886172  CREBBP; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
102881042  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
102897365  TLR4; toll-like receptor 4 precursor [KO:K10160]
102894711  TLR7; toll-like receptor 7 precursor [KO:K05404]
102890488  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
102880867  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
102897349  IRF7; interferon regulatory factor 7 [KO:K09447]
102892998  IL1A; interleukin-1 alpha [KO:K04383]
102893238  IL1B; interleukin-1 beta [KO:K04519]
102895746  IL6; interleukin-6 [KO:K05405]
102887571  IL12A; interleukin-12 subunit alpha [KO:K05406]
102884214  IL12B; interleukin-12 subunit beta [KO:K05425]
102887632  TNF; tumor necrosis factor [KO:K03156]
102892534  CXCL8; interleukin-8 [KO:K10030]
102883786  C-C motif chemokine 2 [KO:K14624]
102878371  CCL5; C-C motif chemokine 5 [KO:K12499]
102880650  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
102897326  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
102893886  interferon alpha-1 [KO:K05414]
102890009  interferon alpha-4 [KO:K05414]
102890512  IFNB1; interferon beta [KO:K05415]
102892040  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
102891485  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
102880365  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
102895629  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
102887834  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
102886603  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
102879640  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
102894320  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
102884844  MX1; interferon-induced GTP-binding protein Mx1 [KO:K14754]
102885101  MX2; interferon-induced GTP-binding protein Mx2 isoform X1 [KO:K14754]
102895190  PML; protein PML isoform X3 [KO:K10054] [EC:2.3.2.-]
102882436  IFNG; interferon gamma precursor [KO:K04687]
102888010  IFNGR1; interferon gamma receptor 1 [KO:K05132]
102877930  IFNGR2; interferon gamma receptor 2 [KO:K05133]
102882079  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
102889981  CIITA; MHC class II transactivator [KO:K08060] [EC:2.7.11.1]
102890716  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
102895822  HLA class II histocompatibility antigen, DQ alpha 2 chain [KO:K06752]
102896083  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
102892493  HLA class II histocompatibility antigen, DM alpha chain isoform X3 [KO:K06752]
102894815  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
102895566  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
102883286  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
102883801  rano class II histocompatibility antigen, A beta chain-like [KO:K06752]
102884055  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
102895309  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
102892903  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
102881234  NLRP3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800]
102888502  PYCARD; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
102885001  IL18; interleukin-18 [KO:K05482]
102878836  IL33; interleukin-33 [KO:K12967]
102879163  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102891637  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X3 [KO:K02649]
102879453  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102889227  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102880320  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102889576  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102885144  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102879337  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102898305  AKT2; LOW QUALITY PROTEIN: RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102881884  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
102894222  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102896272  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102885663  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
102887459  TNFRSF10B; tumor necrosis factor receptor superfamily member 10B [KO:K04722]
102883204  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
102879561  FAS; tumor necrosis factor receptor superfamily member 6 isoform X5 [KO:K04390]
102885752  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
102893401  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
102892511  FADD; FAS-associated death domain protein [KO:K02373]
102878181  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
102887379  BID; BH3-interacting domain death agonist isoform X3 [KO:K04726]
102885135  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
102883540  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
102887036  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
102897294  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
102878001  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
102896364  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
102896575  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
102885895  ADP/ATP translocase 3-like [KO:K05863]
102879159  cytochrome c [KO:K08738]
102893036  cytochrome c, testis-specific-like [KO:K08738]
102897687  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
102878565  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
102897289  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
102898259  CPSF4; cleavage and polyadenylation specificity factor subunit 4 isoform X4 [KO:K14404]
102883822  CPSF4L; putative cleavage and polyadenylation specificity factor subunit 4-like protein [KO:K14404]
102887735  PABPN1L; embryonic polyadenylate-binding protein 2 [KO:K14396]
102888158  nuclear RNA export factor 2 [KO:K14284]
102898356  NXF3; nuclear RNA export factor 3 [KO:K14284]
102887246  NXF1; nuclear RNA export factor 1 [KO:K14284]
102882095  nuclear RNA export factor 2 [KO:K14284]
102897103  NXT1; NTF2-related export protein 1 [KO:K14285]
102879117  NTF2-related export protein 2 [KO:K14285]
102882390  HNRNPUL1; heterogeneous nuclear ribonucleoprotein U-like protein 1 isoform X3 [KO:K15047]
102881845  RAE1; mRNA export factor [KO:K14298]
102892943  NUP98; nuclear pore complex protein Nup98-Nup96 isoform X1 [KO:K14297]
102892916  RSAD2; radical S-adenosyl methionine domain-containing protein 2 [KO:K15045]
102888371  FDPS; farnesyl pyrophosphate synthase isoform X1 [KO:K00787] [EC:2.5.1.1 2.5.1.10]
102887078  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
102893439  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102897122  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102879034  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102895390  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102885749  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102884158  ACTG1; actin, cytoplasmic 2 [KO:K05692]
102884469  ACTB; actin, cytoplasmic 1 [KO:K05692]
102898464  RAB11A; ras-related protein Rab-11A [KO:K07904]
102889088  RAB11B; ras-related protein Rab-11B [KO:K07905]
102881186  XPO1; exportin-1 isoform X1 [KO:K14290]
102887970  KPNA1; importin subunit alpha-5 [KO:K23940]
102894994  KPNA2; importin subunit alpha-1 [KO:K15043]
102898052  KPNA7; importin subunit alpha-8 [KO:K15043]
102882784  KPNA5; importin subunit alpha-6 isoform X1 [KO:K15042]
102893622  KPNA6; importin subunit alpha-7 isoform X3 [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
pale00900  Terpenoid backbone biosynthesis
pale03013  Nucleocytoplasmic transport
pale03015  mRNA surveillance pathway
pale04010  MAPK signaling pathway
pale04110  Cell cycle
pale04144  Endocytosis
pale04210  Apoptosis
pale04620  Toll-like receptor signaling pathway
pale04621  NOD-like receptor signaling pathway
pale04622  RIG-I-like receptor signaling pathway
pale04630  JAK-STAT signaling pathway
pale05416  Viral myocarditis
KO pathway
ko05164   
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