KEGG   PATHWAY: ko05170
Entry
ko05170                     Pathway                                
Name
Human immunodeficiency virus 1 infection
Description
Human immunodeficiency virus type 1 (HIV-1) , the causative agent of AIDS (acquired immunodeficiency syndrome), is a lentivirus belonging to the Retroviridae family. The primary cell surface receptor for HIV-1, the CD4 protein, and the co-receptor for HIV-1, either CCR5 or CXCR4, are found on macrophages and T lymphocytes. At the earliest step, sequential binding of virus envelope (Env) glycoprotein gp120 to CD4 and the co-receptor CCR5 or CXCR4 facilitates HIV-1 entry and has the potential to trigger critical signaling that may favor viral replication. At advanced stages of the disease, HIV-1 infection results in dramatic induction of T-cell (CD4+ T and CD8+ T cell) apoptosis both in infected and uninfected bystander T cells, a hallmark of HIV-1 pathogenesis. On the contrary, macrophages are resistant to the cytopathic effect of HIV-1 and produce virus for longer periods of time.
Class
Human Diseases; Infectious disease: viral
Pathway map
ko05170  Human immunodeficiency virus 1 infection
ko05170

Disease
H00406  Acquired immunodeficiency syndrome (AIDS)
H01563  HIV infection
Drug
D10707  Fostemsavir (USAN)
D10708  Fostemsavir tromethamine (USAN)
D10734  Temsavir (USAN/INN)
D12626  Zinlirvimab (USAN/INN)
D12630  Teropavimab (USAN/INN)
Orthology
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01116  PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11]
K02087  CDK1, CDC2; cyclin-dependent kinase 1 [EC:2.7.11.22 2.7.11.23]
K02158  BAD; Bcl-2-antagonist of cell death
K02159  BAX; apoptosis regulator BAX
K02161  BCL2; apoptosis regulator Bcl-2
K02183  CALM; calmodulin
K02187  CASP3; caspase 3 [EC:3.4.22.56]
K02216  CHEK1; serine/threonine-protein kinase CHEK1 [EC:2.7.11.1]
K02373  FADD; FAS-associated death domain protein
K02580  NFKB1; nuclear factor NF-kappa-B p105 subunit
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K02677  PRKCA; classical protein kinase C alpha type [EC:2.7.11.13]
K02833  HRAS; GTPase HRas
K02861  RIPK1, RIP1; receptor-interacting serine/threonine-protein kinase 1 [EC:2.7.11.1]
K03094  SKP1, CBF3D; S-phase kinase-associated protein 1
K03156  TNF, TNFA; tumor necrosis factor superfamily, member 2
K03158  TNFRSF1A, TNFR1, CD120a; tumor necrosis factor receptor superfamily member 1A
K03171  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein
K03173  TRAF2; TNF receptor-associated factor 2 [EC:2.3.2.27]
K03175  TRAF6; TNF receptor-associated factor 6 [EC:2.3.2.27]
K03347  CUL1, CDC53; cullin 1
K03362  FBXW1_11, BTRC, beta-TRCP; F-box and WD-40 domain protein 1/11
K03868  RBX1, ROC1; E3 ubiquitin-protein ligase RBX1 [EC:2.3.2.32]
K03872  ELOC, TCEB1; elongin-C
K03873  ELOB, TCEB2; elongin-B
K04180  CCR5, CD195; C-C chemokine receptor type 5
K04189  CXCR4, CD184; C-X-C chemokine receptor type 4
K04347  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04348  PPP3C, CNA; serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16]
K04366  RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04379  FOS; proto-oncogene protein c-fos
K04389  TNFSF6, FASL, CD178; tumor necrosis factor ligand superfamily member 6
K04390  TNFRSF6, FAS, CD95; tumor necrosis factor receptor superfamily member 6
K04392  RAC1; Ras-related C3 botulinum toxin substrate 1
K04398  CASP8; caspase 8 [EC:3.4.22.61]
K04399  CASP9; caspase 9 [EC:3.4.22.62]
K04403  MAP3K7IP1, TAB1; TAK1-binding protein 1
K04404  MAP3K7IP2, TAB2; TAK1-binding protein 2
K04409  PAK1; p21-activated kinase 1 [EC:2.7.11.1]
K04410  PAK2; p21-activated kinase 2 [EC:2.7.11.1]
K04427  MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25]
K04431  MAP2K7, MKK7; mitogen-activated protein kinase kinase 7 [EC:2.7.12.2]
K04432  MAP2K3, MKK3; mitogen-activated protein kinase kinase 3 [EC:2.7.12.2]
K04433  MAP2K6, MKK6; mitogen-activated protein kinase kinase 6 [EC:2.7.12.2]
K04438  CRK, CRKII; C-crk adapter molecule crk
K04440  JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K04441  P38; p38 MAP kinase [EC:2.7.11.24]
K04446  NFATC1, NFAT2, NFATC; nuclear factor of activated T-cells, cytoplasmic 1
K04448  JUN; transcription factor AP-1
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04467  IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K04534  GNAO, G-ALPHA-O; guanine nucleotide-binding protein G(o) subunit alpha
K04536  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
K04537  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2
K04538  GNB4; guanine nucleotide-binding protein subunit beta-4
K04539  GNB5; guanine nucleotide-binding protein subunit beta-5
K04540  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
K04541  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
K04542  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
K04543  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
K04544  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8
K04545  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
K04546  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
K04547  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13
K04548  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1
K04549  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
K04570  BCL2L1, bcl-xL; Bcl-2-like 1 (apoptosis regulator Bcl-X)
K04630  GNAI; guanine nucleotide-binding protein G(i) subunit alpha
K04634  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha
K04635  GNA11; guanine nucleotide-binding protein subunit alpha-11
K04688  RPS6KB; ribosomal protein S6 kinase beta [EC:2.7.11.1]
K04726  BID; BH3 interacting domain death agonist
K04728  ATM, TEL1; serine-protein kinase ATM [EC:2.7.11.1]
K04729  MYD88; myeloid differentiation primary response protein MyD88
K04730  IRAK1; interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1]
K04733  IRAK4; interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1]
K04734  NFKBIA; NF-kappa-B inhibitor alpha
K04735  RELA; transcription factor p65
K04958  ITPR1; inositol 1,4,5-triphosphate receptor type 1
K04959  ITPR2; inositol 1,4,5-triphosphate receptor type 2
K04960  ITPR3; inositol 1,4,5-triphosphate receptor type 3
K05141  TNFRSF1B, TNFR2, CD120b; tumor necrosis factor receptor superfamily member 1B
K05410  TBK1; TANK-binding kinase 1 [EC:2.7.11.10]
K05411  IRF3; interferon regulatory factor 3
K05414  IFNA; interferon alpha
K05415  IFNB; interferon beta
K05653  ABCB2, TAP1; ATP-binding cassette, subfamily B (MDR/TAP), member 2 [EC:7.4.2.14]
K05654  ABCB3, TAP2; ATP-binding cassette, subfamily B (MDR/TAP), member 3 [EC:7.4.2.14]
K05725  PTK2, FAK; focal adhesion kinase 1 [EC:2.7.10.2]
K05733  PAK3, MRX30; p21-activated kinase 3 [EC:2.7.11.1]
K05734  PAK4; p21-activated kinase 4 [EC:2.7.11.1]
K05735  PAK6; p21-activated kinase 6 [EC:2.7.11.1]
K05736  PAK5, PAK7; p21-activated kinase 5 [EC:2.7.11.1]
K05743  LIMK1; LIM domain kinase 1 [EC:2.7.11.1]
K05744  LIMK2; LIM domain kinase 2 [EC:2.7.11.1]
K05760  PXN; paxillin
K05765  CFL; cofilin
K05859  PLCG2; phosphatidylinositol phospholipase C, gamma-2 [EC:3.1.4.11]
K05867  CDC25C; M-phase inducer phosphatase 3 [EC:3.1.3.48]
K05868  CCNB1; G2/mitotic-specific cyclin-B1
K05871  PTK2B, FAK2; focal adhesion kinase 2 [EC:2.7.10.2]
K06268  PPP3R, CNB; serine/threonine-protein phosphatase 2B regulatory subunit
K06450  CD3D; T-cell surface glycoprotein CD3 delta chain
K06451  CD3E; T-cell surface glycoprotein CD3 epsilon chain
K06452  CD3G; T-cell surface glycoprotein CD3 gamma chain
K06453  CD3Z, CD247; CD3Z antigen, zeta polypeptide
K06454  CD4; T-cell surface glycoprotein CD4
K06632  WEE1; wee1-like protein kinase [EC:2.7.11.1]
K06640  ATR; serine/threonine-protein kinase ATR [EC:2.7.11.1]
K06731  BST2, CD317; bone marrow stromal cell antigen 2
K06751  MHC1; MHC class I antigen
K07203  MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1]
K07209  IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K07210  IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma
K07825  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
K07826  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
K07827  KRAS, KRAS2; GTPase KRas
K07828  NRAS; GTPase NRas
K07860  RAC2; Ras-related C3 botulinum toxin substrate 2
K07861  RAC3; Ras-related C3 botulinum toxin substrate 3
K08055  B2M; beta-2-microglobulin
K08056  PDIA3, GRP58; protein disulfide-isomerase A3 [EC:5.3.4.1]
K08057  CALR; calreticulin
K08058  TAPBP; TAP binding protein (tapasin)
K08738  CYC; cytochrome c
K09849  TRAF5; TNF receptor-associated factor 5
K10159  TLR2, CD282; toll-like receptor 2
K10160  TLR4, CD284; toll-like receptor 4
K10609  CUL4; cullin 4
K10610  DDB1; DNA damage-binding protein 1
K10611  RBX2, ROC2, RNF7; RING-box protein 2
K10612  CUL5; cullin 5
K10648  TRIM5; tripartite motif-containing protein 5 [EC:2.3.2.27]
K10784  TRAV; T cell receptor alpha chain V region
K10785  TRBV; T-cell receptor beta chain V region
K11789  DCAF1, VPRBP; DDB1- and CUL4-associated factor 1 [EC:2.7.11.1]
K12391  AP1G1; AP-1 complex subunit gamma-1
K12392  AP1B1; AP-1 complex subunit beta-1
K12393  AP1M; AP-1 complex subunit mu
K12394  AP1S1_2; AP-1 complex subunit sigma 1/2
K12395  AP1S3; AP-1 complex subunit sigma-3
K12654  STING1, TMEM173, MITA; stimulator of interferon genes protein
K14021  BAK, BAK1; Bcl-2 homologous antagonist/killer
K17332  NFATC2, NFAT1, NFATP; nuclear factor of activated T-cells, cytoplasmic 2
K17333  NFATC3, NFAT4; nuclear factor of activated T-cells, cytoplasmic 3
K17334  NFATC4, NFAT3; nuclear factor of activated T-cells, cytoplasmic 4
K17834  CGAS, MB21D1; cyclic GMP-AMP synthase [EC:2.7.7.86]
K18750  APOBEC3; C->U-editing enzyme APOBEC3 [EC:3.5.4.-]
K19258  tat; HIV protein Tat
K19662  PRKCB; classical protein kinase C beta type [EC:2.7.11.13]
K19663  PRKCG; classical protein kinase C gamma type [EC:2.7.11.13]
K21770  CCNB2; G2/mitotic-specific cyclin-B2
K21771  CCNB3; G2/mitotic-specific cyclin-B3
K22202  vpr; HIV virus protein R
K22544  SAMHD1; deoxynucleoside triphosphate triphosphohydrolase SAMHD1 [EC:3.1.5.-]
K22890  vpu; HIV-1 protein Vpu
K22891  nef; HIV protein Nef
K22892  vif; HIV virion infectivity factor
K24266  gp120; HIV envelope glycoprotein gp120
K28445  TAPBPL; tapasin-related protein
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C20640  Cyclic GMP-AMP
Reference
PMID:22749173
  Authors
Evans VA, Khoury G, Saleh S, Cameron PU, Lewin SR
  Title
HIV persistence: chemokines and their signalling pathways.
  Journal
Cytokine Growth Factor Rev 23:151-7 (2012)
DOI:10.1016/j.cytogfr.2012.05.002
Reference
PMID:23806647
  Authors
Abbas W, Herbein G
  Title
Plasma membrane signaling in HIV-1 infection.
  Journal
Biochim Biophys Acta 1838:1132-42 (2014)
DOI:10.1016/j.bbamem.2013.06.020
Reference
PMID:20041213
  Authors
Wu Y, Yoder A
  Title
Chemokine coreceptor signaling in HIV-1 infection and pathogenesis.
  Journal
PLoS Pathog 5:e1000520 (2009)
DOI:10.1371/journal.ppat.1000520
Reference
PMID:22085380
  Authors
Choi WT, Duggineni S, Xu Y, Huang Z, An J
  Title
Drug discovery research targeting the CXC chemokine receptor 4 (CXCR4).
  Journal
J Med Chem 55:977-94 (2012)
DOI:10.1021/jm200568c
Reference
PMID:21321123
  Authors
Vorster PJ, Guo J, Yoder A, Wang W, Zheng Y, Xu X, Yu D, Spear M, Wu Y
  Title
LIM kinase 1 modulates cortical actin and CXCR4 cycling and is activated by HIV-1 to initiate viral infection.
  Journal
J Biol Chem 286:12554-64 (2011)
DOI:10.1074/jbc.M110.182238
Reference
PMID:15817946
  Authors
Das SR, Jameel S
  Title
Biology of the HIV Nef protein.
  Journal
Indian J Med Res 121:315-32 (2005)
Reference
PMID:24822052
  Authors
Roy N, Pacini G, Berlioz-Torrent C, Janvier K
  Title
Mechanisms underlying HIV-1 Vpu-mediated viral egress.
  Journal
Front Microbiol 5:177 (2014)
DOI:10.3389/fmicb.2014.00177
Reference
PMID:22090097
  Authors
Magadan JG, Bonifacino JS
  Title
Transmembrane domain determinants of CD4 Downregulation by HIV-1 Vpu.
  Journal
J Virol 86:757-72 (2012)
DOI:10.1128/JVI.05933-11
Reference
PMID:26056579
  Authors
Kumar A, Herbein G
  Title
The macrophage: a therapeutic target in HIV-1 infection.
  Journal
Mol Cell Ther 2:10 (2014)
DOI:10.1186/2052-8426-2-10
Reference
PMID:20672047
  Authors
Yokota S, Okabayashi T, Fujii N
  Title
The battle between virus and host: modulation of Toll-like receptor signaling pathways by virus infection.
  Journal
Mediators Inflamm 2010:184328 (2010)
DOI:10.1155/2010/184328
Reference
PMID:26628325
  Authors
Sauter D, Kirchhoff F
  Title
HIV replication: a game of hide and sense.
  Journal
Curr Opin HIV AIDS 11:173-81 (2016)
DOI:10.1097/COH.0000000000000233
Reference
PMID:25988887
  Authors
Altfeld M, Gale M Jr
  Title
Innate immunity against HIV-1 infection.
  Journal
Nat Immunol 16:554-62 (2015)
DOI:10.1038/ni.3157
Reference
PMID:28358311
  Authors
Pasquereau S, Kumar A, Herbein G
  Title
Targeting TNF and TNF Receptor Pathway in HIV-1 Infection: from Immune Activation to Viral Reservoirs.
  Journal
Viruses 9:64 (2017)
DOI:10.3390/v9040064
Reference
PMID:18178131
  Authors
Herbein G, Khan KA
  Title
Is HIV infection a TNF receptor signalling-driven disease?
  Journal
Trends Immunol 29:61-7 (2008)
DOI:10.1016/j.it.2007.10.008
Reference
PMID:24453421
  Authors
Kumar A, Abbas W, Herbein G
  Title
TNF and TNF receptor superfamily members in HIV infection: new cellular targets for therapy?
  Journal
Mediators Inflamm 2013:484378 (2013)
DOI:10.1155/2013/484378
Reference
PMID:23986795
  Authors
Abbas W, Herbein G
  Title
T-Cell Signaling in HIV-1 Infection.
  Journal
Open Virol J 7:57-71 (2013)
DOI:10.2174/1874357920130621001
Reference
PMID:21368875
  Authors
Cummins NW, Badley AD
  Title
Mechanisms of HIV-associated lymphocyte apoptosis: 2010.
  Journal
Cell Death Dis 1:e99 (2010)
DOI:10.1038/cddis.2010.77
Reference
PMID:12766761
  Authors
Gougeon ML
  Title
Apoptosis as an HIV strategy to escape immune attack.
  Journal
Nat Rev Immunol 3:392-404 (2003)
DOI:10.1038/nri1087
Reference
PMID:21994747
  Authors
Fevrier M, Dorgham K, Rebollo A
  Title
CD4+ T cell depletion in human immunodeficiency virus (HIV) infection: role of apoptosis.
  Journal
Viruses 3:586-612 (2011)
DOI:10.3390/v3050586
Reference
PMID:11237054
  Authors
Ross TM
  Title
Using death to one's advantage: HIV modulation of apoptosis.
  Journal
Leukemia 15:332-41 (2001)
DOI:10.1038/sj.leu.2402028
Reference
PMID:22767237
  Authors
Hurley JH, Bonifacino JS
  Title
Nef-arious goings-on at the Golgi.
  Journal
Nat Struct Mol Biol 19:661-2 (2012)
DOI:10.1038/nsmb.2304
Reference
PMID:21762823
  Authors
Wonderlich ER, Leonard JA, Collins KL
  Title
HIV immune evasion disruption of antigen presentation by the HIV Nef protein.
  Journal
Adv Virus Res 80:103-27 (2011)
DOI:10.1016/B978-0-12-385987-7.00005-1
Reference
PMID:20594957
  Authors
Laguette N, Bregnard C, Benichou S, Basmaciogullari S
  Title
Human immunodeficiency virus (HIV) type-1, HIV-2 and simian immunodeficiency virus Nef proteins.
  Journal
Mol Aspects Med 31:418-33 (2010)
DOI:10.1016/j.mam.2010.05.003
Reference
PMID:27161574
  Authors
Pereira EA, daSilva LL
  Title
HIV-1 Nef: Taking Control of Protein Trafficking.
  Journal
Traffic 17:976-96 (2016)
DOI:10.1111/tra.12412
Reference
PMID:26950141
  Authors
Sugden SM, Bego MG, Pham TN, Cohen EA
  Title
Remodeling of the Host Cell Plasma Membrane by HIV-1 Nef and Vpu: A Strategy to Ensure Viral Fitness and Persistence.
  Journal
Viruses 8:67 (2016)
DOI:10.3390/v8030067
Reference
PMID:24906315
  Authors
Bagga S, Bouchard MJ
  Title
Cell cycle regulation during viral infection.
  Journal
Methods Mol Biol 1170:165-227 (2014)
DOI:10.1007/978-1-4939-0888-2_10
Reference
PMID:15638722
  Authors
Andersen JL, Planelles V
  Title
The role of Vpr in HIV-1 pathogenesis.
  Journal
Curr HIV Res 3:43-51 (2005)
DOI:10.2174/1570162052772988
Reference
PMID:17140287
  Authors
Andersen JL, DeHart JL, Zimmerman ES, Ardon O, Kim B, Jacquot G, Benichou S, Planelles V
  Title
HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT.
  Journal
PLoS Pathog 2:e127 (2006)
DOI:10.1371/journal.ppat.0020127
Reference
PMID:23430691
  Authors
Takaori-Kondo A, Shindo K
  Title
HIV-1 Vif: a guardian of the virus that opens up a new era in the research field of restriction factors.
  Journal
Front Microbiol 4:34 (2013)
DOI:10.3389/fmicb.2013.00034
Reference
PMID:19038776
  Authors
Malim MH
  Title
APOBEC proteins and intrinsic resistance to HIV-1 infection.
  Journal
Philos Trans R Soc Lond B Biol Sci 364:675-87 (2009)
DOI:10.1098/rstb.2008.0185
Reference
PMID:21835787
  Authors
Hultquist JF, Lengyel JA, Refsland EW, LaRue RS, Lackey L, Brown WL, Harris RS
  Title
Human and rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H demonstrate a conserved capacity to restrict Vif-deficient HIV-1.
  Journal
J Virol 85:11220-34 (2011)
DOI:10.1128/JVI.05238-11
Related
pathway
ko03050  Proteasome
ko04010  MAPK signaling pathway
ko04020  Calcium signaling pathway
ko04064  NF-kappa B signaling pathway
ko04110  Cell cycle
ko04141  Protein processing in endoplasmic reticulum
ko04142  Lysosome
ko04150  mTOR signaling pathway
ko04151  PI3K-Akt signaling pathway
ko04210  Apoptosis
ko04612  Antigen processing and presentation
ko04620  Toll-like receptor signaling pathway
ko04623  Cytosolic DNA-sensing pathway
ko04668  TNF signaling pathway
ko04810  Regulation of actin cytoskeleton

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