Cell Collective23300000ModelsTomas Helikarhttps://cellcollective.org/#2738/hiv1-interactions-with-t-cell-signalling-pathway45.76461SBML1Cell Collectivehttps://cellcollective.org/#2738:1/hiv1-interactions-with-t-cell-signalling-pathway<h4>Motivation</h4>Human immunodeficiency virus type 1 (HIV-1) hijacks host cellular processes to replicate within its host. Through interactions with host proteins, it perturbs and interrupts signaling pathways that alter key cellular functions. Although networks of viral-host interactions have been relatively well characterized, the dynamics of the perturbation process is poorly understood. Dynamic models of infection have the potential to provide insights into the HIV-1 host interaction.<h4>Results</h4>We employed a logical signal flow network to model the dynamic interactions between HIV-1 proteins and key human signal transduction pathways necessary for activation of CD4+ T lymphocytes. We integrated viral-host interaction and host signal transduction data into a dynamic logical model comprised of 137 nodes (16 HIV-1 and 121 human proteins) and 336 interactions collected from the HIV-1 Human Interaction Database. The model reproduced expected patterns of T-cell activation, co-stimulation and co-inhibition. After simulations, we identified 26 host cell factors, including MAPK1&3, Ikkb-Ikky-Ikka and PKA, which contribute to the net activation or inhibition of viral proteins. Through in silico knockouts, the model identified a further nine host cell factors, including members of the PI3K signalling pathway that are essential to viral replication. Simulation results intersected with the findings of three siRNA gene knockout studies and identified potential drug targets. Our results demonstrate how viral infection causes the cell to lose control of its signalling system. Logical Boolean modelling therefore provides a useful approach for analysing the dynamics of host-viral interactions with potential applications for drug discovery.<h4>Supplementary information</h4>Supplementary data are available at Bioinformatics online.A logical model of HIV-1 interactions with the T-cell activation signalling pathway.Oyeyemi Oyebode J OJ, Davies Oluwafemi O, Robertson David L DL, Schwartz Jean-Marc JMT cell activation, viral infectious cycle, Materials, dP60, Product, Vps34, Prospecting, T-lymphocyte activation, NetrinA, AIDS Virus, D430049E23Rik, A4, Virus Infection, BcDNA:LD15217, sci, VPS34, 11621, CG18677, Human Immunodeficiency, prevention, Prp4 protein kinase activity, PI-3 kinase, Receptor Mediated Signal Transduction, p110-alpha, Repeat Associated siRNA, dmTAF[[II]]230, Small, ATP-protein transphosphorylase activity, cAMP-dependent protein kinase, T-cell activation, ATP:protein phosphotransferase (non-specific) activity, Ly-4, symptoms, HOW, How, Cell Signaling, gamma sarcoglycan, C, Elkh, Dp60, TFIID TAF250, cel, PI3K_59F, EK6, stru, Pk72A, Pathways, 5' cAMP-dependent protein kinase complex, PI3-kinase activity, SAP-2, l(3)S053606, Sap-2, PI3Kgamma, MCAP, neuroendocrine tumour, Viral Replications, DmelCG6117, 5' cAMP-dependent protein kinase activity, Solute carrier family 6 member 2, Repeat-Associated, medicine, PI3K 68D, SLC6A5, Signal Transduction Pathways, Lymphoid, Infections and Infestations, ATP - 1-phosphatidyl-1D-myo-inositol 3-phosphotransferase activity, single organism signaling, Ikbka, p82 kinase activity, screening, dVps34, Elk, ELK, dTAF[[II]]230, Pathway, preventive therapy, anatomical protrusion, Viral, Neuronally-expressed EPH-related tyrosine kinase, rea, ERK-2, IKBKA, betaIIPKC, cyclic AMP-dependent protein kinase complex, TAF200, CG42341, p50alpha, SAP2, IKK-beta, pka-C1, CG2699, DmelCG5373, signal transduction by trans-phosphorylation, Short, neuroendocrine neoplasm, Incentive, Wee-kinase activity, TCF16, DmIKKgamma, and release, C530050K14, Norepinephrine transporter, dIKK, type-1 PI3K, sarcoglycan, RII[[DR]], Lymphoid Cell, pka-c1, activation, Acquired Immune Deficiency Syndrome Virus, CG11621, Viral Replication, PKA C, Lymphadenopathy-Associated, Disincentive, IKK-gamma, non-specific serine/threonine protein kinase activity, signs, Infection and Infestation, CD4mut, Dmel_CG12452, pka-RII, INSDC_feature:gene, Repeat Associated, DmelCG4141, human, F8A5_4, C78273, APDS, DmelCG18657, DmelCG4379, Replications, signaling pathway, PKA RII, Taf250, Material, 35kD dystrophin-associated glycoprotein, serine-specific protein kinase activity, PkaC1, PI3KBETA, Cells, PKAcA, HIPK2, cytidine 3', RII, Epa, Wee 1-like kinase activity, adenosine 3', TAF230, human immunodeficiency virus infectious disease, 9030612K14Rik, PKAC1, p44erk1, AW488255, glycogen synthase A kinase activity, glycogen synthase kinase 3 activity, HTLV-III, PKA-C3, PKA-C1, dIKK-gamma, BcDNA:GM01761, phosphorylase b kinase kinase activity, Human, Signal Transduction, PIK3, AA407128, dVps34/PI3K59F, Pi3Kp60, Pka-RI, DmIKK-gamma, PI3K-dp110, Immunodeficiency Virus Type 1, Small Scan RNA, Gene Products, l(2)cos[[1]], Prkm1, Cek6, Prkm3, dPI3K, anon-92Ed, Human T-Cell Leukemia Virus Type III, MAM, gamma-SG, ribosomal protein S6 kinase II activity, Man, ERK, PRKM1, class I, ERP, APUDoma, Erp, PRKM2, protein-serine kinase activity, Human T-Lymphotropic Virus Type III, scnRNA, Motivations, Pka-C, anatomical systems, dTAF[[II]]250, cell, egress, STK32, Signal, Signal Pathways, Pi3Kp110, Human T Cell Leukemia Virus Type III, clinical infection, Signal Transduction Pathway, erk, ikk-beta, P110BETA, Short Hairpin, dTAF250, 5'-cyclophosphate-dependent protein kinase activity, drugs, Cos, PI3K21B, CdkA, protein-cysteine kinase activity, Trans Acting siRNA, Hpr kinase activity, Lymphadenopathy-Associated Viruses, STK22, Disincentives, MCM, Signal Pathway, DRI, NET, Net, tasiRNA, Cpk, Pharmaceuticals, Viral Infection, PKA Cl, Products, Human Immunodeficiency Virus, RNA, Trans-Acting, C130099E04Rik, findings, Esrk1, AA414921, 35 kDa dystrophin-associated glycoprotein, class II, type III phosphoinositide 3-kinase activity, Proteins, maturation, Receptor-Mediated Signal Transductions, CG3263, shRNA, CdkR, BG:DS00004.13, protein serine kinase activity, neuroendocrine tumor, qkr, l(3)S090417, net, Cell, PI(3)K, SGCG, protein phosphokinase activity, cpk, Small Hairpin RNA, Short Interfering, dTAF230, PI3K-92E/Dp110, IKKgamma, PIK3C1, cyclic AMP-dependent protein kinase activity, pkA, PKA, Pka, Discovery, PKC, CWS5, T-cell differentiation antigen L3T4, Immunodeficiency Virus, KH93F, mapk2, mapk1, TAF[[II]]250/230, signalling cascade, IKK-alpha, intrinsic catalyst activity, protein kinase p58 activity, AIDS virus, Lymphoid Cells, viral assembly, serine/threonine protein kinase activity, Taf[[II]]250, Small Interfering RNA, pka, pka C1, pKA, dr[[1]], ikkb, PKA C3, AIDS Viruses, DMDA1, IKK1, Pharmaceutic Preparations, IKK2, Dmikkgamma, prophylaxis, P42MAPK, DmelCG11621, 5'-cAMP-dependent protein kinase activity, CG16910, IKKA, dsk1, IKKB, 5'-cyclic monophosphate-responsive protein kinase activity, atypical PKC activity, signalling, DmelCG42341, Gene Proteins, PKA CI, caPI3K, AU018647, CLOVE, signalling process, DmVps34, siRNA, control, IMD14, IMD15, PI3K_68D, PI3K-92D, l(2)01272, Dmp110, virulence, ikk2, Pharmaceutical Products, p44mapk, protein serine-threonine kinase activity, netrin A, Human T Cell Lymphotropic Virus Type III, Repeat-Associated siRNA, glycogen synthase kinase activity, MGC130048, 6353, host organism, Human T-Cell Lymphotropic Virus Type III, Signal Transductions, Dmel_CG3263, T-cell surface antigen T4/Leu-3, protein kinase A activity, CG5373, ATVPS34, Small Hairpin, Infestations and Infections, p42mapk, PI3K, Dp110, Virus Disease, CG12452, Lymphadenopathy Associated Virus, L3T4, PHOSPHATIDYLINOSITOL 3-KINASE, Virus Replications, NFKBIKB, Trans Acting, NFKBIKA, DmelCG2699, Human Immunodeficiency Virus Type 1, F8A5.4, Pharmaceutical Product, Virus, Virus Infections, p110alpha, Dpck, mitogen-activated protein kinase activity, phosphatidylinositol 3-kinase activity, RI, mpk1, Ikka, prevention and control, Human immunodeficiency virus, IKKg, l(3)j5D5, KEY, Key, signal transduction by protein phosphorylation, 24B, viral infection, Man (Taxonomy), Viral Diseases, reference sample, Pi3K92D, CG4141, CG4379, catalyst activity, 3', Pi3k, Fbx24, Chuk1, CG15862, PI[[3]]K, CG10293, INSDC_feature:ncRNA, Raf kinase activity, Drug Prospecting., Viral Gene Products, preventive measures, l(3)j5B5, serine kinase activity, p55alpha, AI256658, atypical protein kinase C activity, Pharmaceutical, signaling process, CT27014, NET1, gamma-sarcoglycan, mitogen-activated S6 kinase activity, protein-aspartyl kinase activity, Pi3K, PI3k, Transductions, netA, MCMTC, Interfering RNA, MNK1, PI3K68D, 0904/17, Trans-Acting siRNA, T-cell surface antigen T4|Leu-3, Mapk, P110DELTA, PtdIns-3-kinase activity, Modern, SG-gamma, signal transduction by conformational transition, ERK1, ERK2, mapk1a, Erk2, 9330129L11, infections, TAFII-250, TAF250/230, results, vacuolar protein sorting 34, dPIK, 1-phosphatidylinositol 3-kinase activity, M phase-specific cdc2 kinase activity, sigma virus replication, signaling cascade, TAFII250, p41mapk, AIDS, pka-R1, SZ1, MAPK, Small Scan, 5'-cAMP-dependent protein kinase complex, Kenny, Cos-1, Diseases, EPH-like kinase 6, Genetic Materials, Pharmaceutic, Short Interfering RNA, Transduction, serine protein kinase activity, Hairpin RNA, Scan, erk2, mapk, Genetic Material, 5-23, phosphorylase B kinase kinase activity, protein glutamyl kinase activity, p85alpha, T lymphocyte activation, Viral Infections, System, T-cell surface glycoprotein CD4, Viral Disease, CG6117, p38, lytic viral life cycle, hEK6, PI3K 68_D, gamma (35kDa dystrophin-associated glycoprotein), CG17603, TAF[[II]], hydroxyalkyl-protein kinase activity, WEE1Hu, p110D, DMDA, DmelCG16910, ATP:protein phosphotransferase (cAMP-dependent) activity, spine, SR3-5, p41, dPKA, epsilon PKC, p40, Acquired Immunodeficiency Syndrome Virus, p44, Viral Protein, Cistron, anon-EST:Liang-2.39, p120-PI3K, Dcpk, droPIK57, Incentives, Signal Transduction Systems, ribosomal S6 protein kinase activity, calcium/phospholipid-dependent protein kinase activity, d230, biological signaling, human being, SGCG_HUMAN, P62, PI3K92E, Receptor-Mediated, Human immunodeficiency virus 1, Gene, Pk?5, Pi3K_59F, Signal Transduction System, PKA-C-3, dTAFII250, type I phosphatidylinositol kinase activity, EfW1, TYPE, phosphatidylinositol 3-kinase, protrusion, netrin, DAGA4, Short Hairpin RNA, Homo sapiens, Hek6, dmTAF1, p60, Taf230, Scan RNA, 35DAG, viral replication, serine(threonine) protein kinase activity, PHOSPATIDYLINOSITOL 3-KINASE, dmIKKgamma, p42-MAPK, BG02142, IKK[[gamma]], AMPK, SCG3, 18304, Dp110/PI3K, ENSMUSG00000074119, T-antigen kinase activity, PI3K-68D/E, TAF250, Drugs, galactosyltransferase-associated kinase activity, Taf200, Fbxo24, Genetic, l(3)s2612, Viruses, PKAR, PkaR, Infections, xp42, Tyrosine-protein kinase receptor EPH-2, Immunodeficiency Viruses, Taf1p, PKa-R2, PKa-R1, PI3'K, PKAc, Infestation and Infection, Erk-1, protein kinase (phosphorylating) activity, signalling pathway, PKA-R1, DmelCG15862, PI3K-68D, PKA-R2, 2.7.10.1, IKK, Raf-1, Etrp, DmelCG10293, Dc0, signal transduction by cis-phosphorylation, HIV, NAT1, Preparation, Human Immunodeficiency Viruses, TAF, casein kinase (phosphorylating) activity, PKA-RI, Lymphocyte, Controlled, Lymphadenopathy-Associated Virus, dP110, Disease, Controlling, ert1, TAF[[II]]250, Human T Lymphotropic Virus Type III, 6330412C24Rik, Cos1, 5'-cyclophosphate-dependent protein kinase complex, l(2)s4402, p120, clone 2.39, drug, DC0, prkm2, EPH tyrosine kinase 2, prkm1, DC2, dPKA-RI, p110, l(3)84Ab, Vps34p, Cistrons, LGMD2C, cos1, twitchin kinase activity, Viral Gene Proteins, PKAi, ATP:1-phosphatidyl-1D-myo-inositol 3-phosphotransferase activity, PKAr, vps34, Receptor-Mediated Signal Transduction, p230, Protein, Systems, AP50 kinase activity, Infection, dp110, dcO, DCO, Dco, TFIID, PI3CG, Replication, Data Base, Pka-RII, who, PI-3-K, threonine-specific protein kinase activity, PI3K-59F, TAF[[II]]230, PI3K-Dp110, dco, class III, TAF[II]250, Who/How, MAPK2, MAPK1, p110gamma, CG18657, PKA-RII, LAV-HTLV-III, Protein Gene Products, Drug, Preparations, DmelCG17603, HIV-I, ERT1, EPHT2, ERT2, Modern Man, SCARMD2, ikkbeta, qkr[93F], CD4, A-kinase activity, Pharmaceutical Preparation, TAF1Human, signal transduction by protein phosphorylation, T cell activation, signaling cascade, signalling pathway, HIV-I, signaling pathway, Human Immunodeficiency Virus Type 1, T lymphocyte activation, T-lymphocyte activation, Immunodeficiency Virus Type 1, T-cell activation, Human immunodeficiency virus 1, signal transduction by conformational transition, signal transduction by cis-phosphorylation, signalling cascade, signal transduction by trans-phosphorylation.signal transduction by protein phosphorylation, T-cell, Thymus-Dependent Lymphocytes, T-Cells, Thymus-Dependent, Human immunodeficiency virus 1, signal transduction by conformational transition, T, Lymphocytes, T-Lymphocyte, Cell, Thymus-Dependent Lymphocyte, signal transduction by trans-phosphorylation., Human, T Cells, signaling cascade, signalling pathway, T cell, HIV-I, signaling pathway, T Lymphocyte, Human Immunodeficiency Virus Type 1, T-Cell, mature T cell, Immunodeficiency Virus Type 1, Cells, signal transduction by cis-phosphorylation, T Cell, signalling cascade, immature T cell, T Lymphocytes, T lymphocyte, Thymus Dependent Lymphocytes, LymphocyteT cell activation, viral infectious cycle, Host Microbial Interface, Materials, dP60, Microbe-Host Interactions, Product, Vps34, Prospecting, T-lymphocyte activation, NetrinA, D430049E23Rik, Virus Infection, BcDNA:LD15217, sci, VPS34, 11621, Host-Virus, CG18677, prevention, Prp4 protein kinase activity, PI-3 kinase, Receptor Mediated Signal Transduction, p110-alpha, Repeat Associated siRNA, dmTAF[[II]]230, Viral Host Interactions, Small, Microbiota-Host Interactions, ATP-protein transphosphorylase activity, cAMP-dependent protein kinase, T-cell activation, ATP:protein phosphotransferase (non-specific) activity, Ly-4, symptoms, HOW, How, Cell Signaling, Virus-Host Interaction, Host-Bacteria Interactions, C, Elkh, Dp60, TFIID TAF250, cel, PI3K_59F, Host-Bacteria, human immunodeficiency virus type 1, EK6, stru, Pk72A, Pathways, 5' cAMP-dependent protein kinase complex, PI3-kinase activity, SAP-2, l(3)S053606, Sap-2, Microbiota Host Interactions, PI3Kgamma, Virus-Host Interactions, Viral-Host Interactions, MCAP, neuroendocrine tumour, Viral Replications, DmelCG6117, 5' cAMP-dependent protein kinase activity, Solute carrier family 6 member 2, Repeat-Associated, medicine, Host Microbe Interaction, PI3K 68D, SLC6A5, Host-Microbe Interaction, Microbe Host Interactions, Signal Transduction Pathways, Lymphoid, Infections and Infestations, ATP - 1-phosphatidyl-1D-myo-inositol 3-phosphotransferase activity, human immunodeficiency virus-1 HIV-1, single organism signaling, Ikbka, p82 kinase activity, screening, dVps34, Elk, ELK, dTAF[[II]]230, Pathway, preventive therapy, anatomical protrusion, Viral, Neuronally-expressed EPH-related tyrosine kinase, rea, ERK-2, IKBKA, betaIIPKC, cyclic AMP-dependent protein kinase complex, TAF200, CG42341, p50alpha, SAP2, Host Fungal Interactions, IKK-beta, pka-C1, CG2699, DmelCG5373, signal transduction by trans-phosphorylation, Short, neuroendocrine neoplasm, Incentive, Wee-kinase activity, human immunodeficiency virus type 1 HIV 1, TCF16, DmIKKgamma, Interaction, and release, C530050K14, Norepinephrine transporter, dIKK, type-1 PI3K, RII[[DR]], Lymphoid Cell, pka-c1, activation, Host-Virus Interaction, CG11621, Viral Replication, PKA C, Disincentive, IKK-gamma, non-specific serine/threonine protein kinase activity, signs, Infection and Infestation, CD4mut, Dmel_CG12452, pka-RII, INSDC_feature:gene, Repeat Associated, DmelCG4141, human, F8A5_4, C78273, APDS, Host-Microbial Interface, DmelCG18657, DmelCG4379, Replications, signaling pathway, PKA RII, Taf250, Material, serine-specific protein kinase activity, PkaC1, PI3KBETA, Cells, PKAcA, HIPK2, cytidine 3', RII, Epa, Wee 1-like kinase activity, adenosine 3', TAF230, 9030612K14Rik, PKAC1, p44erk1, AW488255, glycogen synthase A kinase activity, Host-Microbial Interactions, glycogen synthase kinase 3 activity, PKA-C3, PKA-C1, dIKK-gamma, BcDNA:GM01761, phosphorylase b kinase kinase activity, Human, Signal Transduction, PIK3, AA407128, dVps34/PI3K59F, Pi3Kp60, Pka-RI, DmIKK-gamma, PI3K-dp110, Immunodeficiency Virus Type 1, Small Scan RNA, Gene Products, l(2)cos[[1]], Prkm1, Cek6, Prkm3, dPI3K, anon-92Ed, ribosomal protein S6 kinase II activity, Man, human immunodeficiency virus 1 HIV-1, ERK, PRKM1, class I, ERP, APUDoma, Erp, PRKM2, protein-serine kinase activity, scnRNA, Motivations, Pka-C, anatomical systems, dTAF[[II]]250, cell, egress, STK32, Signal, Signal Pathways, Human immunodeficiency virus type 1, Pi3Kp110, clinical infection, Signal Transduction Pathway, erk, ikk-beta, P110BETA, Short Hairpin, dTAF250, 5'-cyclophosphate-dependent protein kinase activity, drugs, Cos, PI3K21B, CdkA, protein-cysteine kinase activity, Bacteria Host Interactions, Trans Acting siRNA, Hpr kinase activity, human immunodeficiency virus type 1 HIV1, STK22, Disincentives, MCM, Signal Pathway, DRI, NET, Net, tasiRNA, Cpk, Pharmaceuticals, Viral Infection, PKA Cl, Products, RNA, Trans-Acting, C130099E04Rik, findings, Esrk1, AA414921, class II, Host Microbiota Interactions, type III phosphoinositide 3-kinase activity, Proteins, maturation, Receptor-Mediated Signal Transductions, CG3263, shRNA, Bacteria Host Interaction, CdkR, BG:DS00004.13, protein serine kinase activity, neuroendocrine tumor, qkr, l(3)S090417, net, Cell, PI(3)K, protein phosphokinase activity, cpk, Small Hairpin RNA, Short Interfering, dTAF230, PI3K-92E/Dp110, IKKgamma, PIK3C1, cyclic AMP-dependent protein kinase activity, pkA, PKA, Pka, Discovery, PKC, CWS5, T-cell differentiation antigen L3T4, KH93F, Virus-Host, mapk2, mapk1, TAF[[II]]250/230, signalling cascade, IKK-alpha, Host Virus Interaction, intrinsic catalyst activity, Microbial Host Interactions, protein kinase p58 activity, Lymphoid Cells, viral assembly, serine/threonine protein kinase activity, Taf[[II]]250, Host-Microbial, Small Interfering RNA, pka, pka C1, pKA, dr[[1]], ikkb, PKA C3, IKK1, Pharmaceutic Preparations, IKK2, Dmikkgamma, prophylaxis, P42MAPK, DmelCG11621, 5'-cAMP-dependent protein kinase activity, CG16910, IKKA, dsk1, IKKB, 5'-cyclic monophosphate-responsive protein kinase activity, atypical PKC activity, signalling, DmelCG42341, Gene Proteins, PKA CI, caPI3K, AU018647, CLOVE, Microbe-Host Interaction, signalling process, DmVps34, siRNA, control, IMD14, IMD15, PI3K_68D, PI3K-92D, l(2)01272, Dmp110, virulence, ikk2, Viral-Host Interaction, Pharmaceutical Products, p44mapk, Interactions, protein serine-threonine kinase activity, netrin A, Repeat-Associated siRNA, glycogen synthase kinase activity, 6353, host organism, Signal Transductions, Dmel_CG3263, T-cell surface antigen T4/Leu-3, protein kinase A activity, CG5373, ATVPS34, Small Hairpin, Host Virus Interactions, Infestations and Infections, p42mapk, PI3K, Dp110, Microbiota-Host Interaction, Virus Disease, CG12452, L3T4, PHOSPHATIDYLINOSITOL 3-KINASE, Virus Replications, NFKBIKB, Trans Acting, NFKBIKA, DmelCG2699, Human Immunodeficiency Virus Type 1, F8A5.4, Bacterial Host Interactions, Pharmaceutical Product, Virus, Virus Infections, pathogenesis, p110alpha, Dpck, mitogen-activated protein kinase activity, Microbe Host Interaction, human immunodeficiency virus HIV-1, phosphatidylinositol 3-kinase activity, RI, mpk1, Ikka, prevention and control, IKKg, l(3)j5D5, KEY, Key, signal transduction by protein phosphorylation, 24B, viral infection, Bacterial-Host Interactions, Man (Taxonomy), Viral Diseases, reference sample, Pi3K92D, CG4141, CG4379, catalyst activity, 3', Pi3k, Fbx24, Chuk1, Host Microbial Interaction, CG15862, PI[[3]]K, CG10293, INSDC_feature:ncRNA, Raf kinase activity, Drug Prospecting., Viral Gene Products, preventive measures, Bacterial-Host Interaction, l(3)j5B5, serine kinase activity, p55alpha, AI256658, human immunodeficiency virus type-1 HIV-1, atypical protein kinase C activity, Pharmaceutical, signaling process, Virus Host Interaction, CT27014, NET1, mitogen-activated S6 kinase activity, protein-aspartyl kinase activity, Pi3K, PI3k, Transductions, netA, MCMTC, Interfering RNA, MNK1, PI3K68D, 0904/17, Trans-Acting siRNA, Host Microbe Interactions, T-cell surface antigen T4|Leu-3, Mapk, P110DELTA, PtdIns-3-kinase activity, Modern, signal transduction by conformational transition, ERK1, ERK2, mapk1a, Erk2, 9330129L11, infections, TAFII-250, TAF250/230, results, vacuolar protein sorting 34, dPIK, 1-phosphatidylinositol 3-kinase activity, M phase-specific cdc2 kinase activity, sigma virus replication, signaling cascade, TAFII250, p41mapk, pka-R1, SZ1, MAPK, Small Scan, 5'-cAMP-dependent protein kinase complex, Kenny, Cos-1, Diseases, EPH-like kinase 6, Genetic Materials, Pharmaceutic, Short Interfering RNA, Transduction, serine protein kinase activity, Hairpin RNA, Scan, erk2, mapk, Genetic Material, Microbial-Host Interactions, 5-23, phosphorylase B kinase kinase activity, Host-Fungal Interaction, protein glutamyl kinase activity, p85alpha, T lymphocyte activation, Viral Infections, System, T-cell surface glycoprotein CD4, Viral Disease, CG6117, p38, Host-Bacteria Interaction, lytic viral life cycle, hEK6, PI3K 68_D, CG17603, TAF[[II]], hydroxyalkyl-protein kinase activity, WEE1Hu, p110D, DmelCG16910, ATP:protein phosphotransferase (cAMP-dependent) activity, spine, SR3-5, p41, dPKA, epsilon PKC, p40, p44, Viral Protein, Cistron, anon-EST:Liang-2.39, Microbial Host Interaction, p120-PI3K, Dcpk, droPIK57, Host Microbiota Interaction, Incentives, Signal Transduction Systems, ribosomal S6 protein kinase activity, calcium/phospholipid-dependent protein kinase activity, d230, biological signaling, human being, P62, PI3K92E, Receptor-Mediated, Human immunodeficiency virus 1, Gene, Pk?5, Pi3K_59F, Signal Transduction System, PKA-C-3, dTAFII250, type I phosphatidylinositol kinase activity, EfW1, phosphatidylinositol 3-kinase, protrusion, netrin, Bacterium-Host Interactions, Short Hairpin RNA, Host-Microbe, Homo sapiens, Hek6, dmTAF1, p60, Taf230, Scan RNA, Host-Fungal Interactions, viral replication, Bacterium Host Interactions, serine(threonine) protein kinase activity, PHOSPATIDYLINOSITOL 3-KINASE, dmIKKgamma, p42-MAPK, human immunodeficiency virus type 1 HIV-1, BG02142, IKK[[gamma]], Microbe-Host, AMPK, 18304, Dp110/PI3K, ENSMUSG00000074119, T-antigen kinase activity, PI3K-68D/E, TAF250, Drugs, galactosyltransferase-associated kinase activity, Microbial-Host Interaction, Host Bacteria Interactions, Taf200, Fbxo24, Genetic, l(3)s2612, PKAR, PkaR, Viruses, Infections, xp42, Tyrosine-protein kinase receptor EPH-2, Taf1p, PKa-R2, Microbial-Host, Bacterium-Host Interaction, PKa-R1, PI3'K, causes, PKAc, Host-Virus Interactions, Microbiota Host Interaction, Infestation and Infection, Erk-1, protein kinase (phosphorylating) activity, signalling pathway, PKA-R1, DmelCG15862, PI3K-68D, PKA-R2, 2.7.10.1, IKK, Host Bacteria Interaction, Raf-1, Etrp, DmelCG10293, causality, Dc0, signal transduction by cis-phosphorylation, NAT1, Preparation, TAF, casein kinase (phosphorylating) activity, PKA-RI, Lymphocyte, Controlled, dP110, Disease, Controlling, ert1, TAF[[II]]250, human immunodeficiency virus type I HIV-1, 6330412C24Rik, Cos1, 5'-cyclophosphate-dependent protein kinase complex, l(2)s4402, p120, clone 2.39, drug, DC0, prkm2, EPH tyrosine kinase 2, prkm1, DC2, dPKA-RI, p110, l(3)84Ab, Vps34p, Virus Host Interactions, Cistrons, cos1, twitchin kinase activity, Viral Gene Proteins, PKAi, ATP:1-phosphatidyl-1D-myo-inositol 3-phosphotransferase activity, PKAr, vps34, Receptor-Mediated Signal Transduction, p230, Protein, Systems, AP50 kinase activity, Infection, dp110, Host-Microbial Interaction, dcO, DCO, Dco, TFIID, PI3CG, Replication, Data Base, Pka-RII, who, HIV-1, PI-3-K, Host-Microbe Interactions, threonine-specific protein kinase activity, PI3K-59F, TAF[[II]]230, PI3K-Dp110, dco, class III, TAF[II]250, Who/How, MAPK2, MAPK1, p110gamma, CG18657, PKA-RII, Protein Gene Products, Drug, Preparations, DmelCG17603, HIV-I, Microbiota-Host, ERT1, EPHT2, ERT2, Modern Man, ikkbeta, qkr[93F], CD4, Host-Microbial Interfaces, A-kinase activity, Pharmaceutical Preparation, TAF123300falseHIV-1 interactions with T Cell Signalling PathwayMotivation: Human immunodeficiency virus type 1 (HIV-1) hijacks host cellular processes to replicate within its host. Through interactions with host proteins, it perturbs and interrupts signaling pathways that alter key cellular functions. Although networks of viralhost interactions have been relatively well characterized, the dynamics of the perturbation process is poorly understood. Dynamic models of infection have the potential to provide insights into the HIV-1 host interaction. Results: We employed a logical signal flow network to model the dynamic interactions between HIV-1 proteins and key human signal transduction pathways necessary for activation of CD4+ T lymphocytes. We integrated viralhost interaction and host signal transduction data into a dynamic logical model comprised of 137 nodes (16 HIV-1 and 121 human proteins) and 336 interactions collected from the HIV-1 Human Interaction Database. The model reproduced expected patterns of T-cell activation, co-stimulation and co-inhibition. After simulations, we identified 26 host cell factors, including MAPK1&3, Ikkb-Ikky-Ikka and PKA, which contribute to the net activation or inhibition of viral proteins. Through in silico knockouts, the model identified a further nine host cell factors, including members of the PI3K signalling pathway that are essential to viral replication. Simulation results intersected with the findings of three siRNA gene knockout studies and identified potential drug targets. Our results demonstrate how viral infection causes the cell to lose control of its signalling system. Logical Boolean modelling therefore provides a useful approach for analysing the dynamics of hostviral interactions with potential applications for drug discovery.2015-03-092019-11-122019-11-12273825431332