Host Interactions with Influenza Factors (Homo sapiens)

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16181, 6, 18, 212211, 131, 9, 17, 2073, 5, 1921cytosolnucleoplasmmitochondrial inner membranemitochondrial intermembrane spaceNUP43 PB1-F2 SLC25A6 PB1-F2: ANT 3ComplexISGylated NS1Nup45 Large latent complexof TGFB1NS1 NUP54 NUP37 NS1homodimer:ImportinTGFB1 Influenza A dsRNA intermediate form NUP35 Importin alpha NS1 dimerKPNB1 NUP214 RANBP2 ImportinNUP133 POM121 NUP210 EIF2AK2 NS1 NDC1 NS1 Homodimer:PKRComplexCPSF4 Dimeric TGFB1TPR AAAS Importin alpha Influenza A dsRNAintermediate formNUP62 NS1 NS1 HomodimerNS1 ImportinNUP85 NUP98-3 CPSF:NS1 ComplexPABPN1 NUP93 NS1:viral dsRNAComplexNUP188 PB1-F2NS1 EIF2AK2NUP205 NS1 NS1:PAB II ComplexNUP155 KPNB1 NUP98-5 Importin alpha NUPL2 NUPL1-2 NS1 CPSF4NUP88 NS1 NAPOM121C SLC25A6RAE1 NUP153 NUP107 ISG15 PABPN1KPNB1 Nuclear Pore Complex(NPC)NUP98-4 SEH1L-2 NUP50 NUP160 TGFB1 108442, 12, 14, 158


Infection of a human host cell with influenza virus triggers an array of host processes that interfere with viral replication, notably the production of type I interferon. The viral NS1 protein plays a central role in these virus-host interactions. View original pathway at:Reactome.


Pathway is converted from Reactome ID: 168253
Reactome version: 61
Reactome Author 
Reactome Author: Gillespie, Marc E

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  1. O'Neill RE, Jaskunas R, Blobel G, Palese P, Moroianu J.; ''Nuclear import of influenza virus RNA can be mediated by viral nucleoprotein and transport factors required for protein import.''; PubMed Europe PMC Scholia
  2. Fortes P, Beloso A, Ortín J.; ''Influenza virus NS1 protein inhibits pre-mRNA splicing and blocks mRNA nucleocytoplasmic transport.''; PubMed Europe PMC Scholia
  3. Suntharalingam M, Wente SR.; ''Peering through the pore: nuclear pore complex structure, assembly, and function.''; PubMed Europe PMC Scholia
  4. Cronshaw JM, Krutchinsky AN, Zhang W, Chait BT, Matunis MJ.; ''Proteomic analysis of the mammalian nuclear pore complex.''; PubMed Europe PMC Scholia
  5. Noah DL, Twu KY, Krug RM.; ''Cellular antiviral responses against influenza A virus are countered at the posttranscriptional level by the viral NS1A protein via its binding to a cellular protein required for the 3' end processing of cellular pre-mRNAS.''; PubMed Europe PMC Scholia
  6. Li N, Ren A, Wang X, Fan X, Zhao Y, Gao GF, Cleary P, Wang B.; ''Influenza viral neuraminidase primes bacterial coinfection through TGF-β-mediated expression of host cell receptors.''; PubMed Europe PMC Scholia
  7. Son KN, Liang Z, Lipton HL.; ''Double-Stranded RNA Is Detected by Immunofluorescence Analysis in RNA and DNA Virus Infections, Including Those by Negative-Stranded RNA Viruses.''; PubMed Europe PMC Scholia
  8. Melén K, Kinnunen L, Fagerlund R, Ikonen N, Twu KY, Krug RM, Julkunen I.; ''Nuclear and nucleolar targeting of influenza A virus NS1 protein: striking differences between different virus subtypes.''; PubMed Europe PMC Scholia
  9. Ori A, Banterle N, Iskar M, Iskar M, Andrés-Pons A, Escher C, Khanh Bui H, Sparks L, Solis-Mezarino V, Rinner O, Bork P, Lemke EA, Beck M.; ''Cell type-specific nuclear pores: a case in point for context-dependent stoichiometry of molecular machines.''; PubMed Europe PMC Scholia
  10. Chen Z, Li Y, Krug RM.; ''Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 3'-end processing machinery.''; PubMed Europe PMC Scholia
  11. Morris SJ, Price GE, Barnett JM, Hiscox SA, Smith H, Sweet C.; ''Role of neuraminidase in influenza virus-induced apoptosis.''; PubMed Europe PMC Scholia
  12. Rabut G, Doye V, Ellenberg J.; ''Mapping the dynamic organization of the nuclear pore complex inside single living cells.''; PubMed Europe PMC Scholia
  13. Cros JF, García-Sastre A, Palese P.; ''An unconventional NLS is critical for the nuclear import of the influenza A virus nucleoprotein and ribonucleoprotein.''; PubMed Europe PMC Scholia
  14. De Marcos Lousa C, Trézéguet V, Dianoux AC, Brandolin G, Lauquin GJ.; ''The human mitochondrial ADP/ATP carriers: kinetic properties and biogenesis of wild-type and mutant proteins in the yeast S. cerevisiae.''; PubMed Europe PMC Scholia
  15. Donelan NR, Basler CF, García-Sastre A.; ''A recombinant influenza A virus expressing an RNA-binding-defective NS1 protein induces high levels of beta interferon and is attenuated in mice.''; PubMed Europe PMC Scholia
  16. Bergmann M, Garcia-Sastre A, Carnero E, Pehamberger H, Wolff K, Palese P, Muster T.; ''Influenza virus NS1 protein counteracts PKR-mediated inhibition of replication.''; PubMed Europe PMC Scholia
  17. Chanturiya AN, Basañez G, Schubert U, Henklein P, Yewdell JW, Zimmerberg J.; ''PB1-F2, an influenza A virus-encoded proapoptotic mitochondrial protein, creates variably sized pores in planar lipid membranes.''; PubMed Europe PMC Scholia
  18. Nemeroff ME, Barabino SM, Li Y, Keller W, Krug RM.; ''Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs.''; PubMed Europe PMC Scholia
  19. Fontoura BM, Blobel G, Matunis MJ.; ''A conserved biogenesis pathway for nucleoporins: proteolytic processing of a 186-kilodalton precursor generates Nup98 and the novel nucleoporin, Nup96.''; PubMed Europe PMC Scholia
  20. Li Y, Chen ZY, Wang W, Baker CC, Krug RM.; ''The 3'-end-processing factor CPSF is required for the splicing of single-intron pre-mRNAs in vivo.''; PubMed Europe PMC Scholia
  21. Shimizu K, Iguchi A, Gomyou R, Ono Y.; ''Influenza virus inhibits cleavage of the HSP70 pre-mRNAs at the polyadenylation site.''; PubMed Europe PMC Scholia


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101952view13:25, 20 November 2018EgonwRemoved an empty reference.
101205view11:10, 1 November 2018ReactomeTeamreactome version 66
100743view20:35, 31 October 2018ReactomeTeamreactome version 65
100287view19:11, 31 October 2018ReactomeTeamreactome version 64
99833view15:56, 31 October 2018ReactomeTeamreactome version 63
99390view14:33, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99087view12:39, 31 October 2018ReactomeTeamreactome version 62
93925view13:45, 16 August 2017ReactomeTeamreactome version 61
93509view11:25, 9 August 2017ReactomeTeamreactome version 61
87137view18:51, 18 July 2016MkutmonOntology Term : 'infectious disease pathway' added !
86605view09:22, 11 July 2016ReactomeTeamreactome version 56
83394view11:06, 18 November 2015ReactomeTeamVersion54
81586view13:07, 21 August 2015ReactomeTeamVersion53
77047view08:34, 17 July 2014ReactomeTeamFixed remaining interactions
76752view12:11, 16 July 2014ReactomeTeamFixed remaining interactions
76077view10:14, 11 June 2014ReactomeTeamRe-fixing comment source
75787view11:31, 10 June 2014ReactomeTeamReactome 48 Update
75137view14:08, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74784view08:52, 30 April 2014ReactomeTeamNew pathway

External references


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NameTypeDatabase referenceComment
AAAS ProteinQ9NRG9 (Uniprot-TrEMBL)
CPSF4 ProteinO95639 (Uniprot-TrEMBL)
CPSF4ProteinO95639 (Uniprot-TrEMBL)
CPSF:NS1 ComplexComplexR-HSA-169074 (Reactome)
Dimeric TGFB1ComplexR-HSA-170852 (Reactome)
EIF2AK2 ProteinP19525 (Uniprot-TrEMBL)
EIF2AK2ProteinP19525 (Uniprot-TrEMBL)
ISG15 ProteinP05161 (Uniprot-TrEMBL)
ISGylated NS1ComplexR-HSA-1169392 (Reactome)
Importin alpha R-HSA-1176065 (Reactome)
Importin alpha R-HSA-1176071 (Reactome)
ImportinComplexR-HSA-1176060 (Reactome)
ImportinComplexR-HSA-1176073 (Reactome)
Influenza A dsRNA intermediate formR-FLU-6790580 (Reactome)
Influenza A dsRNA intermediate form R-FLU-6790580 (Reactome)
KPNB1 ProteinQ14974 (Uniprot-TrEMBL)
Large latent complex of TGFB1ComplexR-HSA-6791037 (Reactome)
NAProteinP03468 (Uniprot-TrEMBL)
NDC1 ProteinQ9BTX1 (Uniprot-TrEMBL)
NS1 homodimer:ImportinComplexR-HSA-1176067 (Reactome)
NS1 Homodimer:PKR ComplexComplexR-HSA-169142 (Reactome)
NS1 HomodimerComplexR-FLU-169145 (Reactome)
NS1 ProteinP03496 (Uniprot-TrEMBL)
NS1 dimerComplexR-FLU-169143 (Reactome)
NS1:PAB II ComplexComplexR-HSA-169102 (Reactome)
NS1:viral dsRNA ComplexComplexR-FLU-169075 (Reactome)
NUP107 ProteinP57740 (Uniprot-TrEMBL)
NUP133 ProteinQ8WUM0 (Uniprot-TrEMBL)
NUP153 ProteinP49790 (Uniprot-TrEMBL)
NUP155 ProteinO75694 (Uniprot-TrEMBL)
NUP160 ProteinQ12769 (Uniprot-TrEMBL)
NUP188 ProteinQ5SRE5 (Uniprot-TrEMBL)
NUP205 ProteinQ92621 (Uniprot-TrEMBL)
NUP210 ProteinQ8TEM1 (Uniprot-TrEMBL)
NUP214 ProteinP35658 (Uniprot-TrEMBL)
NUP35 ProteinQ8NFH5 (Uniprot-TrEMBL)
NUP37 ProteinQ8NFH4 (Uniprot-TrEMBL)
NUP43 ProteinQ8NFH3 (Uniprot-TrEMBL)
NUP50 ProteinQ9UKX7 (Uniprot-TrEMBL)
NUP54 ProteinQ7Z3B4 (Uniprot-TrEMBL)
NUP62 ProteinP37198 (Uniprot-TrEMBL)
NUP85 ProteinQ9BW27 (Uniprot-TrEMBL)
NUP88 ProteinQ99567 (Uniprot-TrEMBL)
NUP93 ProteinQ8N1F7 (Uniprot-TrEMBL)
NUP98-3 ProteinP52948-3 (Uniprot-TrEMBL)
NUP98-4 ProteinP52948-4 (Uniprot-TrEMBL)
NUP98-5 ProteinP52948-5 (Uniprot-TrEMBL)
NUPL1-2 ProteinQ9BVL2-1 (Uniprot-TrEMBL)
NUPL2 ProteinO15504 (Uniprot-TrEMBL)
Nuclear Pore Complex (NPC)ComplexR-HSA-157689 (Reactome)
Nup45 ProteinQ9BVL2-2 (Uniprot-TrEMBL)
PABPN1 ProteinQ86U42 (Uniprot-TrEMBL)
PABPN1ProteinQ86U42 (Uniprot-TrEMBL)
PB1-F2 ProteinP0C0U1 (Uniprot-TrEMBL)
PB1-F2: ANT 3 ComplexComplexR-HSA-169235 (Reactome)
PB1-F2ProteinP0C0U1 (Uniprot-TrEMBL)
POM121 ProteinQ96HA1 (Uniprot-TrEMBL)
POM121C ProteinA8CG34 (Uniprot-TrEMBL)
RAE1 ProteinP78406 (Uniprot-TrEMBL)
RANBP2 ProteinP49792 (Uniprot-TrEMBL)
SEH1L-2 ProteinQ96EE3-2 (Uniprot-TrEMBL)
SLC25A6 ProteinP12236 (Uniprot-TrEMBL)
SLC25A6ProteinP12236 (Uniprot-TrEMBL)
TGFB1 ProteinP01137 (Uniprot-TrEMBL)
TPR ProteinP12270 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
CPSF4R-HSA-168859 (Reactome)
CPSF:NS1 ComplexArrowR-HSA-168859 (Reactome)
Dimeric TGFB1ArrowR-HSA-168865 (Reactome)
EIF2AK2R-HSA-168896 (Reactome)
ISGylated NS1TBarR-HSA-1176059 (Reactome)
ImportinArrowR-HSA-6791035 (Reactome)
ImportinR-HSA-1176059 (Reactome)
Influenza A dsRNA intermediate formR-HSA-168891 (Reactome)
Large latent complex of TGFB1R-HSA-168865 (Reactome)
NAmim-catalysisR-HSA-168865 (Reactome)
NS1 homodimer:ImportinArrowR-HSA-1176059 (Reactome)
NS1 homodimer:ImportinR-HSA-6791035 (Reactome)
NS1 Homodimer:PKR ComplexArrowR-HSA-168896 (Reactome)
NS1 HomodimerArrowR-HSA-6791035 (Reactome)
NS1 HomodimerR-HSA-168859 (Reactome)
NS1 HomodimerR-HSA-168883 (Reactome)
NS1 dimerR-HSA-1176059 (Reactome)
NS1 dimerR-HSA-168891 (Reactome)
NS1 dimerR-HSA-168896 (Reactome)
NS1:PAB II ComplexArrowR-HSA-168883 (Reactome)
NS1:viral dsRNA ComplexArrowR-HSA-168891 (Reactome)
Nuclear Pore Complex (NPC)mim-catalysisR-HSA-1176059 (Reactome)
PABPN1R-HSA-168883 (Reactome)
PB1-F2: ANT 3 ComplexArrowR-HSA-168878 (Reactome)
PB1-F2R-HSA-168878 (Reactome)
R-HSA-1176059 (Reactome) Influenza A virus nonstructural protein 1 (NS1A) is a multifunctional protein that exists as a dimer and is involved in the inhibition of host cell antiviral pre-mRNA processing and counteracts host cell antiviral responses. Unlike most other RNA viruses, influenza viruses replicate in the nucleus of the host cells. NS1A protein carries two nuclear localization signal (NLS) elements and these sequence elements are recognized by importin-alpha/beta. In the cytoplasm NS1A binds to importin-alpha/beta and these protein complexes are then translocated into the nucleus through the nuclear pore complex (NPC). Note:Reactions directly involving interactions of human host proteins with foreign ones are highlighted in red.
R-HSA-168859 (Reactome) Influenza virus's non-structural protein (NS1) binds to the host cell's cleavage and host polyadenylation specificity factor (CPSF), inhibiting the ability of CPSF to bind to pre-mRNAs and thus preventing efficient 3' end processing and export of host cell mRNAs out of the nucleus.
R-HSA-168865 (Reactome) Influenza A virus induces apoptosis in a variety of ways including by activation of host TGF-beta by viral neuraminidase (NA).
R-HSA-168878 (Reactome) Influenza A virus induces apoptosis in a variety of ways including binding of viral PB1-F2 to host mitochondrial adenine nucleotide translocator 3 (ANT3).
R-HSA-168883 (Reactome) The influenza virus non-structural protein 1 (NS1) binds to the host cell's poly(A)-binding protein II (PABII) thus preventing PABII from properly extending the poly-A tail of pre-mRNA within the host cell nucleus. These pre-mRNAs are then prevented from exiting the nucleus.
R-HSA-168891 (Reactome) The ability of viral non-structural protein 1 (NS1) to sequester dsRNA is believed to be one of the primary mechanisms by which NS1 prevents activation of downstream anti-viral signaling pathways.
R-HSA-168896 (Reactome) Influenza virus inhibits the host double-stranded-RNA-activated protein kinase (PKR) by a couple of mechanisms. One of those steps is the direct binding of PKR by the viral non-structural protein NS1.
R-HSA-6791035 (Reactome) Once the NS1 homodimer is imported into the nucleus, the importin complex releases the NS1 homodimer.
SLC25A6R-HSA-168878 (Reactome)
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