KEGG   PATHWAY: ko05164
ko05164                     Pathway                                
Influenza A
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.
Human Diseases; Infectious disease: viral
Pathway map
ko05164  Influenza A

H00398  Influenza
H00399  Avian influenza
D00777  Amantadine hydrochloride (JP18/USP)
D00900  Oseltamivir phosphate (JAN/USP)
D00901  Rimantadine hydrochloride (USP)
D00902  Zanamivir (USP/INN)
D01937  Zanamivir hydrate (JAN)
D03829  Peramivir (USAN/INN)
D07441  Amantadine (INN)
D08306  Oseltamivir (INN)
D08483  Rimantadine (INN)
D09410  Laninamivir (INN)
D09537  Favipiravir (JAN/USAN/INN)
D09547  Laninamivir octanoate hydrate (JAN)
D10153  Radavirsen (USAN)
D11021  Baloxavir marboxil (JAN/USAN/INN)
D11278  Baloxavir (USAN)
D11287  Pimodivir (USAN/INN)
D11367  Pimodivir hydrochloride (USAN)
D11381  Gedivumab (USAN)
K19251  Influenza A virus hemagglutinin
K19392  Influenza A/B virus neuraminidase [EC:]
K19394  Influenza A virus matrix protein 2
K19393  Influenza A/B virus matrix protein 1
K19391  Influenza virus nucleoprotein
K19390  Influenza virus polymerase acidic protein
K19389  Influenza virus RNA-directed RNA polymerase catalytic subunit [EC:]
K19388  Influenza virus polymerase basic protein 2
K19396  Influenza A virus non-structural protein 1
K19397  Influenza A virus protein PB1-F2
K19395  Influenza A virus nuclear export protein
K01340  tryptase [EC:]
K01315  plasminogen [EC:]
K01312  trypsin [EC:]
K09633  transmembrane protease serine 2 [EC:]
K09635  transmembrane protease serine 4 [EC:3.4.21.-]
K09641  transmembrane protease serine 11D [EC:3.4.21.-]
K19662  classical protein kinase C beta type [EC:]
K14216  2'-5'-oligoadenylate synthetase [EC:]
K01165  ribonuclease L
K09507  DnaJ homolog subfamily B member 1
K09523  DnaJ homolog subfamily C member 3
K16195  eukaryotic translation initiation factor 2-alpha kinase 2 [EC:]
K03237  translation initiation factor 2 subunit 1
K10652  tripartite motif-containing protein 25 [EC:]
K12646  ATP-dependent RNA helicase DDX58 [EC:]
K12647  interferon-induced helicase C domain-containing protein 1 [EC:]
K12653  NLR family member X1
K12648  mitochondrial antiviral-signaling protein
K04467  inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:]
K07209  inhibitor of nuclear factor kappa-B kinase subunit beta [EC:]
K07210  inhibitor of nuclear factor kappa-B kinase subunit gamma
K02581  NF-kappa-B inhibitor beta
K04734  NF-kappa-B inhibitor alpha
K02580  nuclear factor NF-kappa-B p105 subunit
K04735  transcription factor p65
K21348  calcium-binding and coiled-coil domain-containing protein 2
K05401  toll-like receptor 3
K05842  toll-like receptor adapter molecule 1
K03174  TNF receptor-associated factor 3
K05410  TANK-binding kinase 1 [EC:]
K07211  inhibitor of nuclear factor kappa-B kinase subunit epsilon [EC:]
K05411  interferon regulatory factor 3
K04498  E1A/CREB-binding protein [EC:]
K10160  toll-like receptor 4
K05404  toll-like receptor 7
K04729  myeloid differentiation primary response protein MyD88
K04733  interleukin-1 receptor-associated kinase 4 [EC:]
K09447  interferon regulatory factor 7
K04383  interleukin 1 alpha
K04519  interleukin 1 beta
K05405  interleukin 6
K05406  interleukin 12A
K05425  interleukin 12B
K03156  tumor necrosis factor superfamily, member 2
K10030  interleukin 8
K14624  C-C motif chemokine 2
K12499  C-C motif chemokine 5
K12671  C-X-C motif chemokine 10
K06490  intercellular adhesion molecule 1
K05414  interferon alpha
K05415  interferon beta
K05130  interferon receptor 1
K05131  interferon receptor 2
K11217  Janus kinase 1 [EC:]
K11219  non-receptor tyrosine-protein kinase TYK2 [EC:]
K04696  suppressor of cytokine signaling 3
K11220  signal transducer and activator of transcription 1
K11221  signal transducer and activator of transcription 2
K04693  interferon regulatory factor 9
K14754  interferon-induced GTP-binding protein Mx
K12968  double-stranded RNA-specific adenosine deaminase [EC:]
K10054  E3 SUMO-protein ligase PML [EC:2.3.2.-]
K04687  interferon gamma
K05132  interferon gamma receptor 1
K05133  interferon gamma receptor 2
K04447  Janus kinase 2 [EC:]
K08060  MHC class II transactivator [EC:]
K06752  MHC class II antigen
K12800  NACHT, LRR and PYD domains-containing protein 3
K12799  apoptosis-associated speck-like protein containing a CARD
K01370  caspase 1 [EC:]
K05482  interleukin 18
K12967  interleukin 33
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:]
K04456  RAC serine/threonine-protein kinase [EC:]
K10152  G1/S-specific cyclin-D3
K02089  cyclin-dependent kinase 4 [EC:]
K02091  cyclin-dependent kinase 6 [EC:]
K04721  tumor necrosis factor ligand superfamily member 10
K04722  tumor necrosis factor receptor superfamily member 10A/B
K04389  tumor necrosis factor ligand superfamily member 6
K04390  tumor necrosis factor receptor superfamily member 6
K03158  tumor necrosis factor receptor superfamily member 1A
K03171  tumor necrosis factor receptor type 1-associated DEATH domain protein
K02373  FAS-associated death domain protein
K04398  caspase 8 [EC:]
K04726  BH3 interacting domain death agonist
K02159  apoptosis regulator BAX
K14021  Bcl-2 homologous antagonist/killer
K05862  voltage-dependent anion channel protein 1
K05863  solute carrier family 25 (mitochondrial adenine nucleotide translocator), member 4/5/6/31
K08738  cytochrome c
K02084  apoptotic protease-activating factor
K04399  caspase 9 [EC:]
K02187  caspase 3 [EC:]
K14404  cleavage and polyadenylation specificity factor subunit 4
K14396  polyadenylate-binding protein 2
K14284  nuclear RNA export factor
K14285  NTF2-related export protein 1/2
K15047  heterogeneous nuclear ribonucleoprotein U-like protein 1
K14298  mRNA export factor
K14297  nuclear pore complex protein Nup98-Nup96
K15045  radical S-adenosyl methionine domain-containing protein 2
K00787  farnesyl diphosphate synthase [EC:]
K02677  classical protein kinase C alpha type [EC:]
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:]
K04368  mitogen-activated protein kinase kinase 1 [EC:]
K04369  mitogen-activated protein kinase kinase 2 [EC:]
K04371  mitogen-activated protein kinase 1/3 [EC:]
K05692  actin beta/gamma 1
K07904  Ras-related protein Rab-11A
K07905  Ras-related protein Rab-11B
K14290  exportin-1
K23940  importin subunit alpha-5
K15043  importin subunit alpha-1/8
K15042  importin subunit alpha-6/7
C00027  Hydrogen peroxide
C00080  H+
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Edinger TO, Pohl MO, Stertz S
Entry of influenza A virus: host factors and antiviral targets.
J Gen Virol 95:263-77 (2014)
Kido H, Okumura Y, Takahashi E, Pan HY, Wang S, Chida J, Le TQ, Yano M
Host envelope glycoprotein processing proteases are indispensable for entry into human cells by seasonal and highly pathogenic avian influenza viruses.
J Mol Genet Med 3:167-75 (2008)
Ramakrishnan B, Viswanathan K, Tharakaraman K, Dancik V, Raman R, Babcock GJ, Shriver Z, Sasisekharan R
A Structural and Mathematical Modeling Analysis of the Likelihood of Antibody-Dependent Enhancement in Influenza.
Trends Microbiol 24:933-943 (2016)
Thanh TT, van Doorn HR, de Jong MD
Human H5N1 influenza: current insight into pathogenesis.
Int J Biochem Cell Biol 40:2671-4 (2008)
Michael P, Brabant D, Bleiblo F, Ramana CV, Rutherford M, Khurana S, Tai TC, Kumar A, Kumar A
Influenza A induced cellular signal transduction pathways.
J Thorac Dis 5 Suppl 2:S132-41 (2013)
Hale BG, Albrecht RA, Garcia-Sastre A
Innate immune evasion strategies of influenza viruses.
Future Microbiol 5:23-41 (2010)
Sharma K, Tripathi S, Ranjan P, Kumar P, Garten R, Deyde V, Katz JM, Cox NJ, Lal RB, Sambhara S, Lal SK
Influenza A virus nucleoprotein exploits Hsp40 to inhibit PKR activation.
PLoS One 6:e20215 (2011)
Ehrhardt C, Seyer R, Hrincius ER, Eierhoff T, Wolff T, Ludwig S
Interplay between influenza A virus and the innate immune signaling.
Microbes Infect 12:81-7 (2010)
van de Sandt CE, Kreijtz JH, Rimmelzwaan GF
Evasion of influenza A viruses from innate and adaptive immune responses.
Viruses 4:1438-76 (2012)
Long JS, Mistry B, Haslam SM, Barclay WS
Host and viral determinants of influenza A virus species specificity.
Nat Rev Microbiol 17:67-81 (2019)
Chen X, Liu S, Goraya MU, Maarouf M, Huang S, Chen JL
Host Immune Response to Influenza A Virus Infection.
Front Immunol 9:320 (2018)
Lu X, Masic A, Li Y, Shin Y, Liu Q, Zhou Y
The PI3K/Akt pathway inhibits influenza A virus-induced Bax-mediated apoptosis by negatively regulating the JNK pathway via ASK1.
J Gen Virol 91:1439-49 (2010)
Ichinohe T, Iwasaki A, Hasegawa H
Innate sensors of influenza virus: clues to developing better intranasal vaccines.
Expert Rev Vaccines 7:1435-45 (2008)
Le Sage V, Cinti A, Amorim R, Mouland AJ
Adapting the Stress Response: Viral Subversion of the mTOR Signaling Pathway.
Viruses 8:E152 (2016)
Fan Y, Sanyal S, Bruzzone R
Breaking Bad: How Viruses Subvert the Cell Cycle.
Front Cell Infect Microbiol 8:396 (2018)
Varga ZT, Palese P
The influenza A virus protein PB1-F2: killing two birds with one stone?
Virulence 2:542-6 (2011)
Atkin-Smith GK, Duan M, Chen W, Poon IKH
The induction and consequences of Influenza A virus-induced cell death.
Cell Death Dis 9:1002 (2018)
Nogales A, Martinez-Sobrido L, Topham DJ, DeDiego ML
Modulation of Innate Immune Responses by the Influenza A NS1 and PA-X Proteins.
Viruses 10:E708 (2018)
Dai X, Zhang L, Hong T
Host cellular signaling induced by influenza virus.
Sci China Life Sci 54:68-74 (2011)
Li J, Yu M, Zheng W, Liu W
Nucleocytoplasmic shuttling of influenza A virus proteins.
Viruses 7:2668-82 (2015)
Dou D, Revol R, Ostbye H, Wang H, Daniels R
Influenza A Virus Cell Entry, Replication, Virion Assembly and Movement.
Front Immunol 9:1581 (2018)
Paterson D, Fodor E
Emerging roles for the influenza A virus nuclear export protein (NEP).
PLoS Pathog 8:e1003019 (2012)
ko00900  Terpenoid backbone biosynthesis
ko03013  Nucleocytoplasmic transport
ko03015  mRNA surveillance pathway
ko04010  MAPK signaling pathway
ko04110  Cell cycle
ko04144  Endocytosis
ko04210  Apoptosis
ko04620  Toll-like receptor signaling pathway
ko04621  NOD-like receptor signaling pathway
ko04622  RIG-I-like receptor signaling pathway
ko04630  JAK-STAT signaling pathway
ko05416  Viral myocarditis

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