Host Interactions with Influenza Factors (Homo sapiens)

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1710165, 18, 20, 212, 10, 16, 18151, 8, 136, 11mitochondrial intermembrane spacenucleoplasmmitochondrial inner membranecytosolNUP155 TGFB1 NS1 KPNB1 NUP153 NUP214 NUP43 NS1:viral dsRNAComplexNUP98-4 Nuclear Pore Complex(NPC)PB1-F2 AAAS PB1-F2: ANT 3ComplexNUP93 Importin alpha Nup45 NS1 Homodimer:PKRComplexNUP62 PABPN1ISGylated NS1NUP35 NUP205 ImportinTGFB1 KPNB1 NUP85 NS1 dimerInfluenza A dsRNAintermediate formInfluenza A dsRNA intermediate form NUP160 RANBP2 NS1:PAB II ComplexNS1 NUP107 RAE1 SLC25A6NUP50 NUP133 NS1homodimer:ImportinImportin alpha SLC25A6 Large latent complexof TGFB1NUP54 PABPN1 SEH1L-2 EIF2AK2NS1 PB1-F2NAKPNB1 POM121 NS1 NUP188 NUP88 ISG15 NS1 CPSF4ImportinNUPL2 NUP37 NUPL1-2 NUP210 NS1 HomodimerNUP98-5 CPSF4 Importin alpha POM121C NUP98-3 TPR NS1 NDC1 CPSF:NS1 ComplexNS1 EIF2AK2 NS1 Dimeric TGFB11973, 4, 9, 1271414


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: 66
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
  2. Fortes P, Beloso A, Ortín J.; ''Influenza virus NS1 protein inhibits pre-mRNA splicing and blocks mRNA nucleocytoplasmic transport.''; PubMed Europe PMC
  3. Suntharalingam M, Wente SR.; ''Peering through the pore: nuclear pore complex structure, assembly, and function.''; PubMed Europe PMC
  4. Cronshaw JM, Krutchinsky AN, Zhang W, Chait BT, Matunis MJ.; ''Proteomic analysis of the mammalian nuclear pore complex.''; PubMed Europe PMC
  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
  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
  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
  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
  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
  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
  11. Morris SJ, Price GE, Barnett JM, Hiscox SA, Smith H, Sweet C.; ''Role of neuraminidase in influenza virus-induced apoptosis.''; PubMed Europe PMC
  12. Rabut G, Doye V, Ellenberg J.; ''Mapping the dynamic organization of the nuclear pore complex inside single living cells.''; PubMed Europe PMC
  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
  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
  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
  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
  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
  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
  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
  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
  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


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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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