Entry
Name
Influenza A - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
Ortholog table
Network
Element
N00724 IAV NS1 to oligoadenylate synthetase (OAS)/RNase L pathway
N00725 IAV NS1 to PKR-eIF2alpha signaling pathway
N00726 IAV NP to PKR-eIF2alpha signaling pathway
N00727 IAV NS1 to RIG-I-like receptor signaling pathway
N00728 IAV NS1 to RIG-I-like receptor signaling pathway
N00729 IAV NS1 to RIG-I-like receptor signaling pathway
N00730 IAV NS1 to RIG-I-like receptor signaling pathway
N00732 IAV PB1-F2/PB2 to RIG-I-like receptor signaling pathway
N00734 IAV PB1-F2/PB2 to RIG-I-like receptor signaling pathway
N00736 IAV NS1 to PI3K signaling pathway
N00738 IAV NS1 to IFN signaling pathway
N00741 IAV M2 to cell cycle G1/S
N00743 IAV NS1 to NLRP3 inflammasome signaling pathway
N00744 IAV HA to ERK signaling pathway
N00745 IAV PB1-F2 to intrinsic apoptotic pathway
N00746 IAV NS1 to nuclear export of mRNA
Disease
Drug
D12473 Zapnometinib (USAN/INN)
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
56649 TMPRSS4; transmembrane serine protease 4 [KO:K09635 ] [EC:3.4.21.-]
9407 TMPRSS11D; transmembrane serine protease 11D [KO:K09641 ] [EC:3.4.21.-]
3337 DNAJB1; DnaJ heat shock protein family (Hsp40) member B1 [KO:K09507 ]
5611 DNAJC3; DnaJ heat shock protein family (Hsp40) member C3 [KO:K09523 ]
5610 EIF2AK2; eukaryotic translation initiation factor 2 alpha kinase 2 [KO:K16195 ] [EC:2.7.11.1 ]
1965 EIF2S1; eukaryotic translation initiation factor 2 subunit alpha [KO:K03237 ]
57506 MAVS; mitochondrial antiviral signaling protein [KO:K12648 ]
1147 CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467 ] [EC:2.7.11.10 ]
8517 IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210 ]
4790 NFKB1; nuclear factor kappa B subunit 1 [KO:K02580 ]
5970 RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735 ]
10241 CALCOCO2; calcium binding and coiled-coil domain 2 [KO:K21348 ]
148022 TICAM1; TIR domain containing adaptor molecule 1 [KO:K05842 ]
7187 TRAF3; TNF receptor associated factor 3 [KO:K03174 ]
9641 IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211 ] [EC:2.7.11.10 ]
3661 IRF3; interferon regulatory factor 3 [KO:K05411 ]
4615 MYD88; MYD88 innate immune signal transduction adaptor [KO:K04729 ]
3665 IRF7; interferon regulatory factor 7 [KO:K09447 ]
3576 CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030 ]
6347 CCL2; C-C motif chemokine ligand 2 [KO:K14624 ]
6352 CCL5; C-C motif chemokine ligand 5 [KO:K12499 ]
3627 CXCL10; C-X-C motif chemokine ligand 10 [KO:K12671 ]
3383 ICAM1; intercellular adhesion molecule 1 [KO:K06490 ]
3454 IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130 ]
3455 IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131 ]
9021 SOCS3; suppressor of cytokine signaling 3 [KO:K04696 ]
6772 STAT1; signal transducer and activator of transcription 1 [KO:K11220 ]
6773 STAT2; signal transducer and activator of transcription 2 [KO:K11221 ]
5371 PML; PML nuclear body scaffold [KO:K10054 ] [EC:2.3.2.-]
3459 IFNGR1; interferon gamma receptor 1 [KO:K05132 ]
3460 IFNGR2; interferon gamma receptor 2 [KO:K05133 ]
4261 CIITA; class II major histocompatibility complex transactivator [KO:K08060 ] [EC:2.7.11.1 ]
3108 HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752 ]
3109 HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752 ]
3111 HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752 ]
3112 HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752 ]
3113 HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752 ]
3115 HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752 ]
3117 HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752 ]
3118 HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752 ]
3119 HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752 ]
3122 HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752 ]
3123 HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752 ]
3125 HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752 ]
3126 HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752 ]
3127 HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752 ]
3120 HLA-DQB2; major histocompatibility complex, class II, DQ beta 2 [KO:K06752 ]
114548 NLRP3; NLR family pyrin domain containing 3 [KO:K12800 ]
29108 PYCARD; PYD and CARD domain containing [KO:K12799 ]
5295 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
5296 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
8503 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
8743 TNFSF10; TNF superfamily member 10 [KO:K04721 ]
8797 TNFRSF10A; TNF receptor superfamily member 10a [KO:K04722 ]
8795 TNFRSF10B; TNF receptor superfamily member 10b [KO:K04722 ]
355 FAS; Fas cell surface death receptor [KO:K04390 ]
7132 TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158 ]
8717 TRADD; TNFRSF1A associated via death domain [KO:K03171 ]
8772 FADD; Fas associated via death domain [KO:K02373 ]
637 BID; BH3 interacting domain death agonist [KO:K04726 ]
581 BAX; BCL2 associated X, apoptosis regulator [KO:K02159 ]
578 BAK1; BCL2 antagonist/killer 1 [KO:K14021 ]
7416 VDAC1; voltage dependent anion channel 1 [KO:K05862 ]
291 SLC25A4; solute carrier family 25 member 4 [KO:K05863 ]
292 SLC25A5; solute carrier family 25 member 5 [KO:K05863 ]
293 SLC25A6; solute carrier family 25 member 6 [KO:K05863 ]
83447 SLC25A31; solute carrier family 25 member 31 [KO:K05863 ]
317 APAF1; apoptotic peptidase activating factor 1 [KO:K02084 ]
10898 CPSF4; cleavage and polyadenylation specific factor 4 [KO:K14404 ]
642843 CPSF4L; cleavage and polyadenylation specific factor 4 like [KO:K14404 ]
8106 PABPN1; poly(A) binding protein nuclear 1 [KO:K14396 ]
29107 NXT1; nuclear transport factor 2 like export factor 1 [KO:K14285 ]
55916 NXT2; nuclear transport factor 2 like export factor 2 [KO:K14285 ]
11100 HNRNPUL1; heterogeneous nuclear ribonucleoprotein U like 1 [KO:K15047 ]
4928 NUP98; nucleoporin 98 and 96 precursor [KO:K14297 ]
91543 RSAD2; radical S-adenosyl methionine domain containing 2 [KO:K15045 ]
8766 RAB11A; RAB11A, member RAS oncogene family [KO:K07904 ]
9230 RAB11B; RAB11B, member RAS oncogene family [KO:K07905 ]
3836 KPNA1; karyopherin subunit alpha 1 [KO:K23940 ]
3838 KPNA2; karyopherin subunit alpha 2 [KO:K15043 ]
3841 KPNA5; karyopherin subunit alpha 5 [KO:K15042 ]
Compound
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
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
Reference
Authors
Thanh TT, van Doorn HR, de Jong MD
Title
Human H5N1 influenza: current insight into pathogenesis.
Journal
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
Reference
Authors
Hale BG, Albrecht RA, Garcia-Sastre A
Title
Innate immune evasion strategies of influenza viruses.
Journal
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
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
Reference
Authors
van de Sandt CE, Kreijtz JH, Rimmelzwaan GF
Title
Evasion of influenza A viruses from innate and adaptive immune responses.
Journal
Reference
Authors
Long JS, Mistry B, Haslam SM, Barclay WS
Title
Host and viral determinants of influenza A virus species specificity.
Journal
Reference
Authors
Chen X, Liu S, Goraya MU, Maarouf M, Huang S, Chen JL
Title
Host Immune Response to Influenza A Virus Infection.
Journal
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
Reference
Authors
Ichinohe T, Iwasaki A, Hasegawa H
Title
Innate sensors of influenza virus: clues to developing better intranasal vaccines.
Journal
Reference
Authors
Le Sage V, Cinti A, Amorim R, Mouland AJ
Title
Adapting the Stress Response: Viral Subversion of the mTOR Signaling Pathway.
Journal
Reference
Authors
Fan Y, Sanyal S, Bruzzone R
Title
Breaking Bad: How Viruses Subvert the Cell Cycle.
Journal
Reference
Authors
Varga ZT, Palese P
Title
The influenza A virus protein PB1-F2: killing two birds with one stone?
Journal
Reference
Authors
Atkin-Smith GK, Duan M, Chen W, Poon IKH
Title
The induction and consequences of Influenza A virus-induced cell death.
Journal
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
Reference
Authors
Dai X, Zhang L, Hong T
Title
Host cellular signaling induced by influenza virus.
Journal
Reference
Authors
Li J, Yu M, Zheng W, Liu W
Title
Nucleocytoplasmic shuttling of influenza A virus proteins.
Journal
Reference
Authors
Dou D, Revol R, Ostbye H, Wang H, Daniels R
Title
Influenza A Virus Cell Entry, Replication, Virion Assembly and Movement.
Journal
Reference
Authors
Paterson D, Fodor E
Title
Emerging roles for the influenza A virus nuclear export protein (NEP).
Journal
Related pathway
hsa00900 Terpenoid backbone biosynthesis
hsa04620 Toll-like receptor signaling pathway
hsa04621 NOD-like receptor signaling pathway
hsa04622 RIG-I-like receptor signaling pathway
KO pathway