KEGG   PATHWAY: rno05164
Entry
rno05164                    Pathway                                
Name
Influenza A - Rattus norvegicus (rat)
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
rno05164  Influenza A
rno05164

Disease
H00398  Influenza
H00399  Avian influenza
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
100359600  Kpna2l1; importin subunit alpha-1 [KO:K15043]
100360200  Cpsf4l2; cleavage and polyadenylation specificity factor subunit 4-like [KO:K14404]
100361294  Tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
100361457  Actg1l1; actin, gamma 1 propeptide-like [KO:K05692]
100911527  Ifna4l1; interferon alpha-11-like [KO:K05414]
100912314  [KO:K05414]
100912356  [KO:K05414]
102552980  Fdps-ps3; farnesyl pyrophosphate synthase-like [KO:K00787] [EC:2.5.1.1 2.5.1.10]
102554637  [KO:K01312] [EC:3.4.21.4]
103690254  Try5; trypsin-4 isoform X1 [KO:K01312] [EC:3.4.21.4]
114483  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
116465  Ifngr1; interferon gamma receptor 1 precursor [KO:K05132]
116502  Bak1; bcl-2 homologous antagonist/killer [KO:K14021]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116697  Pabpn1; polyadenylate-binding protein 2 [KO:K14396]
120098222  [KO:K05692]
120099910  [KO:K08738]
134484121  [KO:K00922] [EC:2.7.1.153]
134487075  [KO:K05414]
134487077  [KO:K05414]
156435  Tmprss2; transmembrane protease serine 2 [KO:K09633] [EC:3.4.21.122]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
170915  Ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
192281  Oas1a; 2'-5'-oligoadenylate synthase 1A [KO:K14216] [EC:2.7.7.84]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
24481  Ifnb1; interferon beta precursor [KO:K05415]
24493  Il1a; interleukin-1 alpha [KO:K04383]
24494  Il1b; interleukin-1 beta [KO:K04519]
24498  Il6; interleukin-6 precursor [KO:K05405]
24514  Jak2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
24575  Mx1; interferon-induced GTP-binding protein Mx1 [KO:K14754]
245920  Cxcl10; C-X-C motif chemokine 10 precursor [KO:K12671]
246097  Fas; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390]
246268  Oas1b; inactive 2'-5'-oligoadenylate synthase 1B [KO:K14216] [EC:2.7.7.84]
246756  Tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
246775  Tnfsf10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
24680  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
24691  Prss1; serine protease 1 precursor [KO:K01312] [EC:3.4.21.4]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
24770  Ccl2; C-C motif chemokine 2 precursor [KO:K14624]
24835  Tnf; tumor necrosis factor [KO:K03156]
24887  Bax; apoptosis regulator BAX [KO:K02159]
24981  RT1-Db2; RT1 class II, locus Db2 precursor [KO:K06752]
24984  RT1-DOa; RT1 class II, locus DOa precursor [KO:K06752]
24986  RT1-Ha; RT1 class II, locus Ha precursor [KO:K06752]
25023  Prkcb; protein kinase C beta type isoform 2 [KO:K19662] [EC:2.7.11.13]
25052  Prss2; anionic trypsin-2 precursor [KO:K01312] [EC:3.4.21.4]
25124  Stat1; signal transducer and activator of transcription 1-alpha/beta isoform beta [KO:K11220]
25166  Casp1; caspase-1 [KO:K01370] [EC:3.4.22.36]
25176  Slc25a5; ADP/ATP translocase 2 [KO:K05863]
25193  Ccnd3; G1/S-specific cyclin-D3 [KO:K10152]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25309  Cycs; cytochrome c, somatic [KO:K08738]
25310  Cyct; cytochrome c, testis-specific [KO:K08738]
25385  Faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
25402  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
25464  Icam1; intercellular adhesion molecule 1 precursor [KO:K06490]
25493  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
25625  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A precursor [KO:K03158]
25712  Ifng; interferon gamma precursor [KO:K04687]
266610  Fadd; FAS-associated death domain protein [KO:K02373]
282817  Pycard; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
286911  Prss3b; cationic trypsin-3 precursor [KO:K01312] [EC:3.4.21.4]
286918  Mx2; interferon-induced GTP-binding protein Mx2 [KO:K14754]
286960  1810009J06Rikl; trypsin-4 precursor [KO:K01312] [EC:3.4.21.4]
287362  Nlrp3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800]
287562  Ccl12; C-C motif chemokine ligand 12 precursor [KO:K14624]
287824  Trim80; tripartite motif protein 80 [KO:K10652] [EC:2.3.2.27]
287876  Actg1; actin, cytoplasmic 2 [KO:K05692]
288064  Kpna1; importin subunit alpha-5 [KO:K23940]
288264  Ifnar1; interferon alpha/beta receptor 1 isoform 1 precursor [KO:K05130]
288774  Stat2; signal transducer and activator of transcription 2 [KO:K11221]
290019  Cycsl3; cytochrome c, somatic-like [KO:K08738]
29197  Il18; interleukin-18 [KO:K05482]
29260  Tlr4; toll-like receptor 4 precursor [KO:K10160]
29268  Tpsb2; tryptase beta-2 precursor [KO:K01340] [EC:3.4.21.59]
292892  Irf3; interferon regulatory factor 3 [KO:K05411]
293624  Irf7; interferon regulatory factor 7 [KO:K09447]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
294269  RT1-Da; RT1 class II, locus Da precursor [KO:K06752]
294270  RT1-Db1; rano class II histocompatibility antigen, D-1 beta chain precursor [KO:K06752]
294273  RT1-DMb; RT1 class II, DM beta precursor [KO:K06752]
294274  RT1-DMa; RT1 class II, DM alpha precursor [KO:K06752]
294392  Kpna5; importin subunit alpha-6 [KO:K15042]
296219  Nxt1; NTF2-related export protein 1 [KO:K14285]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
297989  Rig1; antiviral innate immune response receptor RIG-I [KO:K12646] [EC:5.6.2.6]
298205  Ifna4; interferon, alpha 4 precursor [KO:K05414]
298210  Ifna5; interferon alpha-1 precursor [KO:K05414]
298213  Ifna2; interferon alpha family, gene 2 precursor [KO:K05414]
299827  Tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
300177  Irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
301059  Myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
302591  Nxf3; nuclear RNA export factor 3 [KO:K14284]
303479  Calcoco2; calcium-binding and coiled-coil domain-containing protein 2 [KO:K21348]
304277  Cpsf4; cleavage and polyadenylation specificity factor subunit 4 isoform 1 [KO:K14404]
304507  Oas1i; 2 ' -5 ' oligoadenylate synthetase 1I [KO:K14216] [EC:2.7.7.84]
305896  Irf9; interferon regulatory factor 9 [KO:K04693]
307920  Pabpn1l; embryonic polyadenylate-binding protein 2 [KO:K14396]
308653  Nxf2; nuclear RNA export factor 2 isoform X1 [KO:K14284]
309165  Rela; transcription factor p65 [KO:K04735]
309295  Ikbkg; NF-kappa-B essential modulator [KO:K07210]
309361  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
309621  RT1-Ba; rano class II histocompatibility antigen, B alpha chain precursor [KO:K06752]
309622  RT1-Bb; rano class II histocompatibility antigen, B-1 beta chain precursor [KO:K06752]
311430  Mavs; mitochondrial antiviral-signaling protein [KO:K12648]
312273  Prss3bl1; trypsin V-A precursor [KO:K01312] [EC:3.4.21.4]
315352  Nxt2; NTF2-related export protein 2 [KO:K14285]
315599  Nlrx1; NLR family member X1 precursor [KO:K12653]
315713  Pml; PML nuclear body scaffold [KO:K10054] [EC:2.3.2.-]
317468  Tlr7; toll-like receptor 7 [KO:K05404]
359726  Rnasel; 2-5A-dependent ribonuclease [KO:K01165]
360697  Ifngr2; interferon gamma receptor 2 precursor [KO:K05133]
361384  Dnajb1; dnaJ homolog subfamily B member 1 [KO:K09507]
361522  Hnrnpul1; heterogeneous nuclear ribonucleoprotein U-like protein 1 [KO:K15047]
361749  Il33; interleukin-33 [KO:K12967]
362281  Rae1; mRNA export factor [KO:K14298]
362347  Prss3; serine protease 3 precursor [KO:K01312] [EC:3.4.21.4]
362607  Kpna6; importin subunit alpha-7 [KO:K15042]
362788  Traf3; TNF receptor-associated factor 3 [KO:K03174]
363328  Ticam1; TIR domain-containing adapter molecule 1 [KO:K05842]
363938  Oas2; 2'-5'-oligoadenylate synthase 2 [KO:K14216] [EC:2.7.7.84]
363984  Ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
364594  Tlr3; toll-like receptor 3 precursor [KO:K05401]
365542  RT1-DOb; RT1 class II, DO beta isoform 1 [KO:K06752]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
367074  Tmprss4; transmembrane protease serine 4 [KO:K09635] [EC:3.4.21.-]
367149  Bax-ps1; apoptosis regulator BAX-like [KO:K02159]
408247  Try10; trypsin 10 precursor [KO:K01312] [EC:3.4.21.4]
494202  Oas3; 2'-5'-oligoadenylate synthase 3 [KO:K14216] [EC:2.7.7.84]
494338  Trim25; E3 ubiquitin/ISG15 ligase TRIM25 [KO:K10652] [EC:2.3.2.27]
498885  Slc25a6; solute carrier family 25 member 6 [KO:K05863]
499801  Ifih1; interferon-induced helicase C domain-containing protein 1 [KO:K12647] [EC:5.6.2.6]
500491  Ifna16l1; interferon, alpha 16-like 1 precursor [KO:K05414]
500871  Slc25a5l1; ADP/ATP translocase 2-like [KO:K05863]
501621  Nxf7; nuclear RNA export factor 7 [KO:K14284]
502959  Ifna1l1; similar to put. precursor MuIFN-alpha 5 precursor [KO:K05414]
502961  Ifna4l2; similar to Interferon alpha-1 precursor [KO:K05414]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
54244  Crebbp; histone lysine acetyltransferase CREBBP [KO:K04498] [EC:2.3.1.48]
54271  Tpsab1; tryptase precursor [KO:K01340] [EC:3.4.21.59]
54287  Eif2ak2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
54318  Eif2s1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
58918  Casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
58960  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
59087  Nxf1; nuclear RNA export factor 1 [KO:K14284]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
63880  Dnajc3; dnaJ homolog subfamily C member 3 precursor [KO:K09523]
64044  Casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
64546  Il12b; interleukin-12 subunit beta precursor [KO:K05425]
64565  Tmprss11d; transmembrane protease serine 11D isoform a [KO:K09641] [EC:3.4.21.-]
64625  Bid; BH3-interacting domain death agonist [KO:K04726]
65190  Rsad2; S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 [KO:K15045]
679794  Cycsl1; cytochrome c, somatic-like [KO:K08738]
681314  [KO:K02159]
683849  Prss2l1; anionic trypsin-2 [KO:K01312] [EC:3.4.21.4]
686326  Ifnar2; interferon alpha and beta receptor subunit 2 isoform 1 precursor [KO:K05131]
689108  Slc25a31; ADP/ATP translocase 4 [KO:K05863]
690504  Kpna7; importin subunit alpha-8 [KO:K15043]
690675  Cycsl2; cytochrome c, somatic-like [KO:K08738]
690894  Ifna1; interferon alpha family, gene 5 precursor [KO:K05414]
78963  Apaf1; apoptotic protease-activating factor 1 [KO:K02084]
79434  Rab11b; ras-related protein Rab-11B [KO:K07905]
81525  Nfkbib; NF-kappa-B inhibitor beta [KO:K02581]
81635  Adar; double-stranded RNA-specific adenosine deaminase [KO:K12968] [EC:3.5.4.37]
81736  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform 2 [KO:K02580]
81738  Nup98; nuclear pore complex protein Nup98-Nup96 proprotein [KO:K14297]
81780  Ccl5; C-C motif chemokine 5 precursor [KO:K12499]
81822  Actb; actin, cytoplasmic 1 [KO:K05692]
81830  Rab11a; ras-related protein Rab-11A [KO:K07904]
83529  Vdac1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
83791  Fdps; farnesyl pyrophosphate synthase [KO:K00787] [EC:2.5.1.1 2.5.1.10]
84351  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
84405  Il12a; interleukin-12 subunit alpha precursor [KO:K05406]
84598  Jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
85245  Kpna2; importin subunit alpha-1 [KO:K15043]
85252  Xpo1; exportin-1 [KO:K14290]
85253  Plg; plasminogen precursor [KO:K01315] [EC:3.4.21.7]
85333  Slc25a4; ADP/ATP translocase 1 [KO:K05863]
85483  Ciita; MHC class II transactivator isoform 2 [KO:K08060] [EC:2.7.11.1]
89829  Socs3; suppressor of cytokine signaling 3 [KO:K04696]
94201  Cdk4; cyclin-dependent kinase 4 isoform 1 [KO:K02089] [EC:2.7.11.22]
Compound
C00027  Hydrogen peroxide
C00080  H+
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  Authors
Le Sage V, Cinti A, Amorim R, Mouland AJ
  Title
Adapting the Stress Response: Viral Subversion of the mTOR Signaling Pathway.
  Journal
Viruses 8:152 (2016)
DOI:10.3390/v8060152
Reference
  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
  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
  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
  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 10:708 (2018)
DOI:10.3390/v10120708
Reference
  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
  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
  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
  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
rno00900  Terpenoid backbone biosynthesis
rno03013  Nucleocytoplasmic transport
rno03015  mRNA surveillance pathway
rno04010  MAPK signaling pathway
rno04110  Cell cycle
rno04144  Endocytosis
rno04210  Apoptosis
rno04620  Toll-like receptor signaling pathway
rno04621  NOD-like receptor signaling pathway
rno04622  RIG-I-like receptor signaling pathway
rno04630  JAK-STAT signaling pathway
rno05416  Viral myocarditis
KO pathway
ko05164   

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