KEGG PATHWAY: map05167

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

Disease

H00041

Kaposi sarcoma

Reference

PMID:22403573

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

PMID:18948197

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

PMID:21040832

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

PMID:16760382

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

PMID:19230674

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

PMID:16905191

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

PMID:11500830

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

Eur J Immunol 31:2458-66 (2001)
DOI:10.1002/1521-4141(200108)31:8<2458::AID-IMMU2458>3.0.CO;2-L

Reference

PMID:10666184

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

PMID:26431609

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

PMID:10377196

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

PMID:18434408

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

PMID:15692053

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

PMID:15967719

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

PMID:16828973

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

PMID:12032073

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

PMID:10510092

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

PMID:10523854

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

PMID:12890756

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

PMID:20865011

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

PMID:10799607

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

PMID:17166914

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

PMID:18230726

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

PMID:11413168

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

PMID:24710493

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

PMID:10354594

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

PMID:12770701

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

PMID:11960692

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

PMID:15220441

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

PMID:10987301

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

PMID:27518127

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

PMID:15573137

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

PMID:17329974

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

PMID:23028325

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

PMID:10318948

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

PMID:26192396

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

PMID:25187543

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

PMID:17050609

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

PMID:16585191