KEGG   PATHWAY: map05167
Entry
map05167                    Pathway                                
Name
Kaposi sarcoma-associated herpesvirus infection
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
Pathway map
map05167  Kaposi sarcoma-associated herpesvirus infection
map05167

Disease
H00041  Kaposi sarcoma
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
Front Microbiol 3:44 (2012)
DOI:10.3389/fmicb.2012.00044
Reference
  Authors
Liang C, Lee JS, Jung JU
  Title
Immune evasion in Kaposi's sarcoma-associated herpes virus associated oncogenesis.
  Journal
Semin Cancer Biol 18:423-36 (2008)
DOI:10.1016/j.semcancer.2008.09.003
Reference
  Authors
Cai Q, Verma SC, Lu J, Robertson ES
  Title
Molecular biology of Kaposi's sarcoma-associated herpesvirus and related oncogenesis.
  Journal
Adv Virus Res 78:87-142 (2010)
DOI:10.1016/B978-0-12-385032-4.00003-3
Reference
  Authors
Rezaee SA, Cunningham C, Davison AJ, Blackbourn DJ
  Title
Kaposi's sarcoma-associated herpesvirus immune modulation: an overview.
  Journal
J Gen Virol 87:1781-804 (2006)
DOI:10.1099/vir.0.81919-0
Reference
  Authors
Areste C, Blackbourn DJ
  Title
Modulation of the immune system by Kaposi's sarcoma-associated herpesvirus.
  Journal
Trends Microbiol 17:119-29 (2009)
DOI:10.1016/j.tim.2008.12.001
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
Mol Immunol 44:11-22 (2007)
DOI:10.1016/j.molimm.2006.06.018
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
Curr Opin Virol 14:116-28 (2015)
DOI:10.1016/j.coviro.2015.08.016
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
J Exp Med 189:1993-8 (1999)
DOI:10.1084/jem.189.12.1993
Reference
  Authors
Choi YB, Nicholas J
  Title
Autocrine and paracrine promotion of cell survival and virus replication by human herpesvirus 8 chemokines.
  Journal
J Virol 82:6501-13 (2008)
DOI:10.1128/JVI.02396-07
Reference
  Authors
McCormick C, Ganem D
  Title
The kaposin B protein of KSHV activates the p38/MK2 pathway and stabilizes cytokine mRNAs.
  Journal
Science 307:739-41 (2005)
DOI:10.1126/science.1105779
Reference
  Authors
Wang HW, Boshoff C
  Title
Linking Kaposi virus to cancer-associated cytokines.
  Journal
Trends Mol Med 11:309-12 (2005)
DOI:10.1016/j.molmed.2005.06.002
Reference
  Authors
Jarviluoma A, Ojala PM
  Title
Cell signaling pathways engaged by KSHV.
  Journal
Biochim Biophys Acta 1766:140-58 (2006)
DOI:10.1016/j.bbcan.2006.05.001
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
EMBO J 21:2602-15 (2002)
DOI:10.1093/emboj/21.11.2602
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
J Exp Med 190:1025-32 (1999)
DOI:10.1084/jem.190.7.1025
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
Oncogene 18:5738-46 (1999)
DOI:10.1038/sj.onc.1202976
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
J Cell Sci 116:3721-8 (2003)
DOI:10.1242/jcs.00691
Reference
  Authors
Mesri EA, Cesarman E, Boshoff C
  Title
Kaposi's sarcoma and its associated herpesvirus.
  Journal
Nat Rev Cancer 10:707-19 (2010)
DOI:10.1038/nrc2888
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
J Virol 74:5300-9 (2000)
DOI:10.1128/JVI.74.11.5300-5309.2000
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
J Virol 81:2117-27 (2007)
DOI:10.1128/JVI.01961-06
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
Proc Natl Acad Sci U S A 105:1656-61 (2008)
DOI:10.1073/pnas.0707883105
Reference
  Authors
Coscoy L, Ganem D
  Title
A viral protein that selectively downregulates ICAM-1 and B7-2 and modulates T cell costimulation.
  Journal
J Clin Invest 107:1599-606 (2001)
DOI:10.1172/JCI12432
Reference
  Authors
Pratt ZL, Sugden B
  Title
How human tumor viruses make use of autophagy.
  Journal
Cells 1:617-30 (2012)
DOI:10.3390/cells1030617
Reference
  Authors
Schulz TF, Moore PS
  Title
Kaposi's sarcoma-associated herpesvirus: a new human tumor virus, but how?
  Journal
Trends Microbiol 7:196-200 (1999)
DOI:10.1016/S0966-842X(99)01495-X
Reference
PMID:9594662
  Authors
Moore PS, Chang Y
  Title
Antiviral activity of tumor-suppressor pathways: clues from molecular piracy by KSHV.
  Journal
Trends Genet 14:144-50 (1998)
DOI:10.1016/S0168-9525(98)01408-5
Reference
  Authors
Verma SC, Robertson ES
  Title
Molecular biology and pathogenesis of Kaposi sarcoma-associated herpesvirus.
  Journal
FEMS Microbiol Lett 222:155-63 (2003)
DOI:10.1016/S0378-1097(03)00261-1
Reference
  Authors
Jenner RG, Boshoff C
  Title
The molecular pathology of Kaposi's sarcoma-associated herpesvirus.
  Journal
Biochim Biophys Acta 1602:1-22 (2002)
DOI:10.1016/S0304-419X(01)00040-3
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
J Virol 78:7667-76 (2004)
DOI:10.1128/JVI.78.14.7667-7676.2004
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
Curr Opin Virol 20:11-19 (2016)
DOI:10.1016/j.coviro.2016.07.008
Reference
  Authors
Sodhi A, Montaner S, Gutkind JS
  Title
Viral hijacking of G-protein-coupled-receptor signalling networks.
  Journal
Nat Rev Mol Cell Biol 5:998-1012 (2004)
DOI:10.1038/nrm1529
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
Cell Cycle 6:438-43 (2007)
DOI:10.4161/cc.6.4.3843
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
PLoS Pathog 8:e1002927 (2012)
DOI:10.1371/journal.ppat.1002927
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
Proc Natl Acad Sci U S A 96:5704-9 (1999)
DOI:10.1073/pnas.96.10.5704
Reference
  Authors
Sousa-Squiavinato AC, Silvestre RN, Elgui De Oliveira D
  Title
Biology and oncogenicity of the Kaposi sarcoma herpesvirus K1 protein.
  Journal
Rev Med Virol 25:273-85 (2015)
DOI:10.1002/rmv.1843
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
J Virol 88:13161-72 (2014)
DOI:10.1128/JVI.01766-14
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
J Virol 81:42-58 (2007)
DOI:10.1128/JVI.00648-06
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
Cancer Res 66:3658-66 (2006)
DOI:10.1158/0008-5472.CAN-05-3680
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
Virology 428:112-20 (2012)
DOI:10.1016/j.virol.2012.03.013
Reference
  Authors
Purushothaman P, Uppal T, Verma SC
  Title
Molecular biology of KSHV lytic reactivation.
  Journal
Viruses 7:116-53 (2015)
DOI:10.3390/v7010116
Reference
  Authors
Fujimuro M, Hayward SD
  Title
Manipulation of glycogen-synthase kinase-3 activity in KSHV-associated cancers.
  Journal
J Mol Med (Berl) 82:223-31 (2004)
DOI:10.1007/s00109-003-0519-7
Reference
  Authors
Purushothaman P, Dabral P, Gupta N, Sarkar R, Verma SC
  Title
KSHV Genome Replication and Maintenance.
  Journal
Front Microbiol 7:54 (2016)
DOI:10.3389/fmicb.2016.00054
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KO pathway
ko05167   

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