Entry
Name
Human immunodeficiency virus 1 infection - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
hsa05170 Human immunodeficiency virus 1 infection
Ortholog table
Network
Element
N00431 HIV gp120 to CXCR4-GNAI-PI3K-BAD signaling pathway
N00432 HIV gp120 to CXCR4-GNAQ-PLCB/G-calcineurin
N00434 HIV gp120 to CXCR4-GNB/G-RAC signaling pathway
N00436 HIV Tat to TLR2/4-NFKB signaling pathway
N00437 HIV Vpu to TLR2/4-NFKB signaling pathway
N00439 HIV Nef to TLR2/4-MAPK signaling pathway
N00440 HIV Vpu/Vif/Vpr to cGAS-STING signaling pathway
N00441 HIV gp120 to TNF-NFKB signaling pathway
N00442 HIV Nef to TNF-NFKB signaling pathway
N00443 HIV Vpr/Nef/Tat to TNF-NFKB signaling pathway
N00445 HIV Tat/Nef to TNF-p38 signaling pathway
N00447 HIV Vpr/Tat to TNF-JNK signaling pathway
N00448 HIV Tat/Nef to crosstalk between extrinsic and intrinsic apoptotic pathways
N00449 HIV Tat/Nef to crosstalk between extrinsic and intrinsic apoptotic pathways
N00450 HIV Tat to intrinsic apoptotic pathway
N00451 HIV Tat to intrinsic apoptotic pathway
N00452 HIV Nef to intrinsic apoptotic pathway
N00453 HIV Vpr to intrinsic apoptotic pathway
N00454 HIV Vpr to intrinsic apoptotic pathway
N00456 HIV Vpr to CDC25-cell cycle G2M
N00457 HIV Vpr to cell cycle G2M
N00458 HIV Vpr to CDC25-cell cycle G2M
N00460 HIV Vpr to WEE1-cell cycle G2M
N00461 HIV Nef to antigen processing and presentation by MHC class I molecules
Disease
H00406 Acquired immunodeficiency syndrome (AIDS)
Drug
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
8945 BTRC; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362 ]
23291 FBXW11; F-box and WD repeat domain containing 11 [KO:K03362 ]
6500 SKP1; S-phase kinase associated protein 1 [KO:K03094 ]
7852 CXCR4; C-X-C motif chemokine receptor 4 [KO:K04189 ]
1234 CCR5; C-C motif chemokine receptor 5 [KO:K04180 ]
2770 GNAI1; G protein subunit alpha i1 [KO:K04630 ]
2773 GNAI3; G protein subunit alpha i3 [KO:K04630 ]
2771 GNAI2; G protein subunit alpha i2 [KO:K04630 ]
2775 GNAO1; G protein subunit alpha o1 [KO:K04534 ]
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 ]
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 ]
1398 CRK; CRK proto-oncogene, adaptor protein [KO:K04438 ]
1399 CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438 ]
4790 NFKB1; nuclear factor kappa B subunit 1 [KO:K02580 ]
5970 RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735 ]
2353 FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379 ]
3725 JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448 ]
572 BAD; BCL2 associated agonist of cell death [KO:K02158 ]
3265 HRAS; HRas proto-oncogene, GTPase [KO:K02833 ]
3845 KRAS; KRAS proto-oncogene, GTPase [KO:K07827 ]
4893 NRAS; NRAS proto-oncogene, GTPase [KO:K07828 ]
2767 GNA11; G protein subunit alpha 11 [KO:K04635 ]
3708 ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958 ]
3709 ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959 ]
3710 ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960 ]
5534 PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268 ]
5535 PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268 ]
4772 NFATC1; nuclear factor of activated T cells 1 [KO:K04446 ]
4773 NFATC2; nuclear factor of activated T cells 2 [KO:K17332 ]
4775 NFATC3; nuclear factor of activated T cells 3 [KO:K17333 ]
4776 NFATC4; nuclear factor of activated T cells 4 [KO:K17334 ]
2790 GNG10; G protein subunit gamma 10 [KO:K04545 ]
2791 GNG11; G protein subunit gamma 11 [KO:K04546 ]
2792 GNGT1; G protein subunit gamma transducin 1 [KO:K04548 ]
2793 GNGT2; G protein subunit gamma transducin 2 [KO:K04549 ]
7133 TNFRSF1B; TNF receptor superfamily member 1B [KO:K05141 ]
4615 MYD88; MYD88 innate immune signal transduction adaptor [KO:K04729 ]
10454 TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403 ]
23118 TAB2; TGF-beta activated kinase 1 (MAP3K7) binding protein 2 [KO:K04404 ]
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 ]
340061 STING1; stimulator of interferon response cGAMP interactor 1 [KO:K12654 ]
3661 IRF3; interferon regulatory factor 3 [KO:K05411 ]
164668 APOBEC3H; apolipoprotein B mRNA editing enzyme catalytic subunit 3H [KO:K18750 ] [EC:3.5.4.-]
200316 APOBEC3F; apolipoprotein B mRNA editing enzyme catalytic subunit 3F [KO:K18750 ] [EC:3.5.4.-]
100913187 APOBEC3A_B; APOBEC3A and APOBEC3B deletion hybrid [KO:K18750 ] [EC:3.5.4.-]
140564 APOBEC3D; apolipoprotein B mRNA editing enzyme catalytic subunit 3D [KO:K18750 ] [EC:3.5.4.-]
200315 APOBEC3A; apolipoprotein B mRNA editing enzyme catalytic subunit 3A [KO:K18750 ] [EC:3.5.4.-]
27350 APOBEC3C; apolipoprotein B mRNA editing enzyme catalytic subunit 3C [KO:K18750 ] [EC:3.5.4.-]
60489 APOBEC3G; apolipoprotein B mRNA editing enzyme catalytic subunit 3G [KO:K18750 ] [EC:3.5.4.-]
9582 APOBEC3B; apolipoprotein B mRNA editing enzyme catalytic subunit 3B [KO:K18750 ] [EC:3.5.4.-]
25939 SAMHD1; SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 [KO:K22544 ] [EC:3.1.5.-]
684 BST2; bone marrow stromal cell antigen 2 [KO:K06731 ]
7132 TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158 ]
8717 TRADD; TNFRSF1A associated via death domain [KO:K03171 ]
7188 TRAF5; TNF receptor associated factor 5 [KO:K09849 ]
355 FAS; Fas cell surface death receptor [KO:K04390 ]
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 ]
596 BCL2; BCL2 apoptosis regulator [KO:K02161 ]
916 CD3E; CD3 epsilon subunit of T-cell receptor complex [KO:K06451 ]
917 CD3G; CD3 gamma subunit of T-cell receptor complex [KO:K06452 ]
915 CD3D; CD3 delta subunit of T-cell receptor complex [KO:K06450 ]
6890 TAP1; transporter 1, ATP binding cassette subfamily B member [KO:K05653 ] [EC:7.4.2.14 ]
6891 TAP2; transporter 2, ATP binding cassette subfamily B member [KO:K05654 ] [EC:7.4.2.14 ]
3105 HLA-A; major histocompatibility complex, class I, A [KO:K06751 ]
3106 HLA-B; major histocompatibility complex, class I, B [KO:K06751 ]
3107 HLA-C; major histocompatibility complex, class I, C [KO:K06751 ]
3134 HLA-F; major histocompatibility complex, class I, F [KO:K06751 ]
3135 HLA-G; major histocompatibility complex, class I, G [KO:K06751 ]
3133 HLA-E; major histocompatibility complex, class I, E [KO:K06751 ]
162 AP1B1; adaptor related protein complex 1 subunit beta 1 [KO:K12392 ]
164 AP1G1; adaptor related protein complex 1 subunit gamma 1 [KO:K12391 ]
8906 AP1G2; adaptor related protein complex 1 subunit gamma 2 [KO:K12391 ]
8907 AP1M1; adaptor related protein complex 1 subunit mu 1 [KO:K12393 ]
10053 AP1M2; adaptor related protein complex 1 subunit mu 2 [KO:K12393 ]
1174 AP1S1; adaptor related protein complex 1 subunit sigma 1 [KO:K12394 ]
8905 AP1S2; adaptor related protein complex 1 subunit sigma 2 [KO:K12394 ]
130340 AP1S3; adaptor related protein complex 1 subunit sigma 3 [KO:K12395 ]
1642 DDB1; damage specific DNA binding protein 1 [KO:K10610 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference
Authors
Evans VA, Khoury G, Saleh S, Cameron PU, Lewin SR
Title
HIV persistence: chemokines and their signalling pathways.
Journal
Reference
Authors
Abbas W, Herbein G
Title
Plasma membrane signaling in HIV-1 infection.
Journal
Reference
Authors
Wu Y, Yoder A
Title
Chemokine coreceptor signaling in HIV-1 infection and pathogenesis.
Journal
Reference
Authors
Choi WT, Duggineni S, Xu Y, Huang Z, An J
Title
Drug discovery research targeting the CXC chemokine receptor 4 (CXCR4).
Journal
Reference
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
Reference
Authors
Das SR, Jameel S
Title
Biology of the HIV Nef protein.
Journal
Indian J Med Res 121:315-32 (2005)
Reference
Authors
Roy N, Pacini G, Berlioz-Torrent C, Janvier K
Title
Mechanisms underlying HIV-1 Vpu-mediated viral egress.
Journal
Reference
Authors
Magadan JG, Bonifacino JS
Title
Transmembrane domain determinants of CD4 Downregulation by HIV-1 Vpu.
Journal
Reference
Authors
Kumar A, Herbein G
Title
The macrophage: a therapeutic target in HIV-1 infection.
Journal
Reference
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
Reference
Authors
Sauter D, Kirchhoff F
Title
HIV replication: a game of hide and sense.
Journal
Reference
Authors
Altfeld M, Gale M Jr
Title
Innate immunity against HIV-1 infection.
Journal
Reference
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
Reference
Authors
Herbein G, Khan KA
Title
Is HIV infection a TNF receptor signalling-driven disease?
Journal
Reference
Authors
Kumar A, Abbas W, Herbein G
Title
TNF and TNF receptor superfamily members in HIV infection: new cellular targets for therapy?
Journal
Reference
Authors
Abbas W, Herbein G
Title
T-Cell Signaling in HIV-1 Infection.
Journal
Reference
Authors
Cummins NW, Badley AD
Title
Mechanisms of HIV-associated lymphocyte apoptosis: 2010.
Journal
Reference
Authors
Gougeon ML
Title
Apoptosis as an HIV strategy to escape immune attack.
Journal
Reference
Authors
Fevrier M, Dorgham K, Rebollo A
Title
CD4+ T cell depletion in human immunodeficiency virus (HIV) infection: role of apoptosis.
Journal
Reference
Authors
Ross TM
Title
Using death to one's advantage: HIV modulation of apoptosis.
Journal
Reference
Authors
Hurley JH, Bonifacino JS
Title
Nef-arious goings-on at the Golgi.
Journal
Reference
Authors
Wonderlich ER, Leonard JA, Collins KL
Title
HIV immune evasion disruption of antigen presentation by the HIV Nef protein.
Journal
Reference
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
Reference
Authors
Pereira EA, daSilva LL
Title
HIV-1 Nef: Taking Control of Protein Trafficking.
Journal
Reference
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
Reference
Authors
Bagga S, Bouchard MJ
Title
Cell cycle regulation during viral infection.
Journal
Reference
Authors
Andersen JL, Planelles V
Title
The role of Vpr in HIV-1 pathogenesis.
Journal
Reference
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
Reference
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
Reference
Authors
Malim MH
Title
APOBEC proteins and intrinsic resistance to HIV-1 infection.
Journal
Reference
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
Related pathway
hsa04141 Protein processing in endoplasmic reticulum
hsa04612 Antigen processing and presentation
hsa04620 Toll-like receptor signaling pathway
hsa04810 Regulation of actin cytoskeleton
KO pathway
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