Entry
Name
Kaposi sarcoma-associated herpesvirus infection - Homo sapiens (human)
Description
Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is the most recently identified human tumor virus, and is associated with the pathogenesis of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and Multicentric Castleman's disease (MCD). Like all other herpesviruses, KSHV displays two modes of life cycle, latency and lytic replication, which are characterized by the patterns of viral gene expression. Genes expressed in latency (LANA, v-cyclin, v-FLIP, Kaposins A, B and C and viral miRNAs) are mainly thought to facilitate the establishment of life long latency in its host and survival against the host innate, and adaptive immune surveillance mechanisms. Among the viral proteins shown to be expressed during lytic replication are potent signaling molecules such as vGPCR, vIL6, vIRFs, vCCLs, K1 and K15, which have been implicated experimentally in the angiogenic and inflammatory phenotype observed in KS lesions. Several of these latent viral and lytic proteins are known to transform host cells, linking KSHV with the development of severe human malignancies.
Class
Human Diseases; Infectious disease: viral
BRITE hierarchy
Pathway map
hsa05167 Kaposi sarcoma-associated herpesvirus infection
Ortholog table
Network
Element
N00157 KSHV vGPCR to GNB/G-ERK signaling pathway
N00158 KSHV vGPCR to GNB/G-PI3K-AKT signaling pathway
N00159 KSHV K1 to PI3K signaling pathway
N00160 KSHV K1 to RAS-ERK signaling pathway
N00161 KSHV vIRF1/2 to TLR3-IRF3 signaling pathway
N00162 KSHV vIRF3 to TLR3-IRF7 signaling pathway
N00163 KSHV KIE1/2 to TLR3-IRF7 signaling pathway
N00164 KSHV vBCL2 to crosstalk between extrinsic and intrinsic apoptotic pathways
N00165 KSHV vIAP to crosstalk between extrinsic and intrinsic apoptotic pathways
N00166 KSHV vFLIP to crosstalk between extrinsic and intrinsic apoptotic pathways
N00167 KSHV vIRF1/3 to p21-cell cycle G1/S
N00168 KSHV vCyclin to cell cycle G1/S
N00169 KSHV LANA to p21-cell cycle G1/S
N00170 KSHV LANA to cell cycle G1/S
N00171 KSHV vFLIP to NFKB signaling pathway
N00172 KSHV K15 to PLCG-calcineurin signaling pathway
N00173 KSHV K15 to TNF-NFKB signaling pathway
N00174 KSHV vFLIP to TNF-NFKB signaling pathway
N00175 KSHV LANA to Wnt signaling pathway
N00176 KSHV vFLIP to autophagy-vesicle elongation
N00177 KSHV vBCL2 to autophagy-vesicle nucleation
N00178 KSHV vGPCR to GNB/G-PI3K-JNK signaling pathway
N00179 KSHV K1 to PI3K-NFKB signaling pathway
N00180 KSHV K1 to PLCG-calcineurin signaling pathway
N00181 KSHV vIL-6 to Jak-STAT signaling pathway
N00184 KSHV MIR1/2 to antigen processing and presentation by MHC class I molecules
N00185 KSHV MIR2 to cell surface molecule-endocytosis
N00187 KSHV Kaposin B to p38 signaling pathway
N00189 KSHV K15 to JNK signaling pathway
N00212 KSHV vCCL2 to CCR signaling pathway
N00213 KSHV Kaposin to alternative pathway of complement cascade
N00261 KSHV vIRF2 to IFN signaling pathway
N00462 KSHV vCCL1/2/3 to CCR signaling pathway
N01527 KSHV Kaposin to classical/Lectin pathway of complement cascade, C4b breakdown
N01528 KSHV Kaposin to alternative pathway of complement cascade, C3b breakdown
Disease
Drug
D02745 Interferon alfa-2b (USAN)
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
148022 TICAM1; TIR domain containing adaptor molecule 1 [KO:K05842 ]
7187 TRAF3; TNF receptor associated factor 3 [KO:K03174 ]
9641 IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211 ] [EC:2.7.11.10 ]
3665 IRF7; interferon regulatory factor 7 [KO:K09447 ]
3661 IRF3; interferon regulatory factor 3 [KO:K05411 ]
3454 IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130 ]
3455 IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131 ]
6772 STAT1; signal transducer and activator of transcription 1 [KO:K11220 ]
6773 STAT2; signal transducer and activator of transcription 2 [KO:K11221 ]
5610 EIF2AK2; eukaryotic translation initiation factor 2 alpha kinase 2 [KO:K16195 ] [EC:2.7.11.1 ]
1437 CSF2; colony stimulating factor 2 [KO:K05427 ]
1232 CCR3; C-C motif chemokine receptor 3 [KO:K04178 ]
1234 CCR5; C-C motif chemokine receptor 5 [KO:K04180 ]
1230 CCR1; C-C motif chemokine receptor 1 [KO:K04176 ]
1233 CCR4; C-C motif chemokine receptor 4 [KO:K04179 ]
1237 CCR8; C-C motif chemokine receptor 8 [KO:K04183 ]
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 ]
7132 TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158 ]
8717 TRADD; TNFRSF1A associated via death domain [KO:K03171 ]
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 ]
4790 NFKB1; nuclear factor kappa B subunit 1 [KO:K02580 ]
5970 RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735 ]
1026 CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625 ]
5925 RB1; RB transcriptional corepressor 1 [KO:K06618 ]
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 ]
3459 IFNGR1; interferon gamma receptor 1 [KO:K05132 ]
3383 ICAM1; intercellular adhesion molecule 1 [KO:K06490 ]
4277 MICB; MHC class I polypeptide-related sequence B [KO:K07985 ]
9976 CLEC2B; C-type lectin domain family 2 member B [KO:K10071 ]
7311 UBA52; ubiquitin A-52 residue ribosomal protein fusion product 1 [KO:K02927 ]
440738 MAP1LC3C; microtubule associated protein 1 light chain 3 gamma [KO:K10435 ]
81631 MAP1LC3B; microtubule associated protein 1 light chain 3 beta [KO:K10435 ]
84557 MAP1LC3A; microtubule associated protein 1 light chain 3 alpha [KO:K10435 ]
643246 MAP1LC3B2; microtubule associated protein 1 light chain 3 beta 2 [KO:K10435 ]
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 ]
3265 HRAS; HRas proto-oncogene, GTPase [KO:K02833 ]
3845 KRAS; KRAS proto-oncogene, GTPase [KO:K07827 ]
4893 NRAS; NRAS proto-oncogene, GTPase [KO:K07828 ]
3091 HIF1A; hypoxia inducible factor 1 subunit alpha [KO:K08268 ]
3725 JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448 ]
2353 FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379 ]
5294 PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289 ] [EC:2.7.1.153 ]
23533 PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290 ]
146850 PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290 ]
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 ]
57580 PREX1; phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 [KO:K12365 ]
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 ]
3576 CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030 ]
2919 CXCL1; C-X-C motif chemokine ligand 1 [KO:K05505 ]
2920 CXCL2; C-X-C motif chemokine ligand 2 [KO:K05505 ]
2921 CXCL3; C-X-C motif chemokine ligand 3 [KO:K05505 ]
1827 RCAN1; regulator of calcineurin 1 [KO:K17901 ]
7422 VEGFA; vascular endothelial growth factor A [KO:K05448 ]
5155 PDGFB; platelet derived growth factor subunit B [KO:K17386 ]
3572 IL6ST; interleukin 6 cytokine family signal transducer [KO:K05060 ]
6774 STAT3; signal transducer and activator of transcription 3 [KO:K04692 ]
83439 TCF7L1; transcription factor 7 like 1 [KO:K04490 ]
6934 TCF7L2; transcription factor 7 like 2 [KO:K04491 ]
51176 LEF1; lymphoid enhancer binding factor 1 [KO:K04492 ]
1385 CREB1; cAMP responsive element binding protein 1 [KO:K05870 ]
4609 MYC; MYC proto-oncogene, bHLH transcription factor [KO:K04377 ]
Compound
C00350 Phosphatidylethanolamine
C01245 D-myo-Inositol 1,4,5-trisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference
Authors
Lee HR, Brulois K, Wong L, Jung JU
Title
Modulation of Immune System by Kaposi's Sarcoma-Associated Herpesvirus: Lessons from Viral Evasion Strategies.
Journal
Reference
Authors
Liang C, Lee JS, Jung JU
Title
Immune evasion in Kaposi's sarcoma-associated herpes virus associated oncogenesis.
Journal
Reference
Authors
Cai Q, Verma SC, Lu J, Robertson ES
Title
Molecular biology of Kaposi's sarcoma-associated herpesvirus and related oncogenesis.
Journal
Reference
Authors
Rezaee SA, Cunningham C, Davison AJ, Blackbourn DJ
Title
Kaposi's sarcoma-associated herpesvirus immune modulation: an overview.
Journal
Reference
Authors
Areste C, Blackbourn DJ
Title
Modulation of the immune system by Kaposi's sarcoma-associated herpesvirus.
Journal
Reference
Authors
Mark L, Spiller OB, Villoutreix BO, Blom AM
Title
Kaposi's sarcoma-associated herpes virus complement control protein: KCP--complement inhibition and more.
Journal
Reference
Authors
Weber KS, Grone HJ, Rocken M, Klier C, Gu S, Wank R, Proudfoot AE, Nelson PJ, Weber C
Title
Selective recruitment of Th2-type cells and evasion from a cytotoxic immune response mediated by viral macrophage inhibitory protein-II.
Journal
Reference
Authors
Stine JT, Wood C, Hill M, Epp A, Raport CJ, Schweickart VL, Endo Y, Sasaki T, Simmons G, Boshoff C, Clapham P, Chang Y, Moore P, Gray PW, Chantry D
Title
KSHV-encoded CC chemokine vMIP-III is a CCR4 agonist, stimulates angiogenesis, and selectively chemoattracts TH2 cells.
Journal
Blood 95:1151-7 (2000)
Reference
Authors
Schulz TF, Cesarman E
Title
Kaposi Sarcoma-associated Herpesvirus: mechanisms of oncogenesis.
Journal
Reference
Authors
Endres MJ, Garlisi CG, Xiao H, Shan L, Hedrick JA
Title
The Kaposi's sarcoma-related herpesvirus (KSHV)-encoded chemokine vMIP-I is a specific agonist for the CC chemokine receptor (CCR)8.
Journal
Reference
Authors
Choi YB, Nicholas J
Title
Autocrine and paracrine promotion of cell survival and virus replication by human herpesvirus 8 chemokines.
Journal
Reference
Authors
McCormick C, Ganem D
Title
The kaposin B protein of KSHV activates the p38/MK2 pathway and stabilizes cytokine mRNAs.
Journal
Reference
Authors
Wang HW, Boshoff C
Title
Linking Kaposi virus to cancer-associated cytokines.
Journal
Reference
Authors
Jarviluoma A, Ojala PM
Title
Cell signaling pathways engaged by KSHV.
Journal
Reference
Authors
Wang HW, Sharp TV, Koumi A, Koentges G, Boshoff C
Title
Characterization of an anti-apoptotic glycoprotein encoded by Kaposi's sarcoma-associated herpesvirus which resembles a spliced variant of human survivin.
Journal
Reference
Authors
Djerbi M, Screpanti V, Catrina AI, Bogen B, Biberfeld P, Grandien A
Title
The inhibitor of death receptor signaling, FLICE-inhibitory protein defines a new class of tumor progression factors.
Journal
Reference
Authors
Chaudhary PM, Jasmin A, Eby MT, Hood L
Title
Modulation of the NF-kappa B pathway by virally encoded death effector domains-containing proteins.
Journal
Reference
Authors
Field N, Low W, Daniels M, Howell S, Daviet L, Boshoff C, Collins M
Title
KSHV vFLIP binds to IKK-gamma to activate IKK.
Journal
Reference
Authors
Mesri EA, Cesarman E, Boshoff C
Title
Kaposi's sarcoma and its associated herpesvirus.
Journal
Reference
Authors
Ishido S, Wang C, Lee BS, Cohen GB, Jung JU
Title
Downregulation of major histocompatibility complex class I molecules by Kaposi's sarcoma-associated herpesvirus K3 and K5 proteins.
Journal
Reference
Authors
Li Q, Means R, Lang S, Jung JU
Title
Downregulation of gamma interferon receptor 1 by Kaposi's sarcoma-associated herpesvirus K3 and K5.
Journal
Reference
Authors
Thomas M, Boname JM, Field S, Nejentsev S, Salio M, Cerundolo V, Wills M, Lehner PJ
Title
Down-regulation of NKG2D and NKp80 ligands by Kaposi's sarcoma-associated herpesvirus K5 protects against NK cell cytotoxicity.
Journal
Reference
Authors
Coscoy L, Ganem D
Title
A viral protein that selectively downregulates ICAM-1 and B7-2 and modulates T cell costimulation.
Journal
Reference
Authors
Pratt ZL, Sugden B
Title
How human tumor viruses make use of autophagy.
Journal
Reference
Authors
Schulz TF, Moore PS
Title
Kaposi's sarcoma-associated herpesvirus: a new human tumor virus, but how?
Journal
Reference
Authors
Moore PS, Chang Y
Title
Antiviral activity of tumor-suppressor pathways: clues from molecular piracy by KSHV.
Journal
Reference
Authors
Verma SC, Robertson ES
Title
Molecular biology and pathogenesis of Kaposi sarcoma-associated herpesvirus.
Journal
Reference
Authors
Jenner RG, Boshoff C
Title
The molecular pathology of Kaposi's sarcoma-associated herpesvirus.
Journal
Reference
Authors
Foster-Cuevas M, Wright GJ, Puklavec MJ, Brown MH, Barclay AN
Title
Human herpesvirus 8 K14 protein mimics CD200 in down-regulating macrophage activation through CD200 receptor.
Journal
Reference
Authors
Sodhi A, Montaner S, Patel V, Zohar M, Bais C, Mesri EA, Gutkind JS
Title
The Kaposi's sarcoma-associated herpes virus G protein-coupled receptor up-regulates vascular endothelial growth factor expression and secretion through mitogen-activated protein kinase and p38 pathways acting on hypoxia-inducible factor 1alpha.
Journal
Cancer Res 60:4873-80 (2000)
Reference
Authors
Abere B, Schulz TF
Title
KSHV non-structural membrane proteins involved in the activation of intracellular signaling pathways and the pathogenesis of Kaposi's sarcoma.
Journal
Reference
Authors
Sodhi A, Montaner S, Gutkind JS
Title
Viral hijacking of G-protein-coupled-receptor signalling networks.
Journal
Reference
Authors
Montaner S
Title
Akt/TSC/mTOR activation by the KSHV G protein-coupled receptor: emerging insights into the molecular oncogenesis and treatment of Kaposi's sarcoma.
Journal
Reference
Authors
Bala K, Bosco R, Gramolelli S, Haas DA, Kati S, Pietrek M, Havemeier A, Yakushko Y, Singh VV, Dittrich-Breiholz O, Kracht M, Schulz TF
Title
Kaposi's sarcoma herpesvirus K15 protein contributes to virus-induced angiogenesis by recruiting PLCgamma1 and activating NFAT1-dependent RCAN1 expression.
Journal
Reference
Authors
Lagunoff M, Majeti R, Weiss A, Ganem D
Title
Deregulated signal transduction by the K1 gene product of Kaposi's sarcoma-associated herpesvirus.
Journal
Reference
Authors
Sousa-Squiavinato AC, Silvestre RN, Elgui De Oliveira D
Title
Biology and oncogenicity of the Kaposi sarcoma herpesvirus K1 protein.
Journal
Reference
Authors
Havemeier A, Gramolelli S, Pietrek M, Jochmann R, Sturzl M, Schulz TF
Title
Activation of NF-kappaB by the Kaposi's sarcoma-associated herpesvirus K15 protein involves recruitment of the NF-kappaB-inducing kinase, IkappaB kinases, and phosphorylation of p65.
Journal
Reference
Authors
Brinkmann MM, Pietrek M, Dittrich-Breiholz O, Kracht M, Schulz TF
Title
Modulation of host gene expression by the K15 protein of Kaposi's sarcoma-associated herpesvirus.
Journal
Reference
Authors
Wang L, Dittmer DP, Tomlinson CC, Fakhari FD, Damania B
Title
Immortalization of primary endothelial cells by the K1 protein of Kaposi's sarcoma-associated herpesvirus.
Journal
Reference
Authors
Morris VA, Punjabi AS, Wells RC, Wittkopp CJ, Vart R, Lagunoff M
Title
The KSHV viral IL-6 homolog is sufficient to induce blood to lymphatic endothelial cell differentiation.
Journal
Reference
Authors
Purushothaman P, Uppal T, Verma SC
Title
Molecular biology of KSHV lytic reactivation.
Journal
Reference
Authors
Fujimuro M, Hayward SD
Title
Manipulation of glycogen-synthase kinase-3 activity in KSHV-associated cancers.
Journal
Reference
Authors
Purushothaman P, Dabral P, Gupta N, Sarkar R, Verma SC
Title
KSHV Genome Replication and Maintenance.
Journal
Related pathway
hsa04610 Complement and coagulation cascades
hsa04620 Toll-like receptor signaling pathway
hsa04650 Natural killer cell mediated cytotoxicity
KO pathway