Skip to main content
SpringerLink
Log in

Molecular Biology of Human Herpesvirus 8: Novel Functions and Virus–Host Interactions Implicated in Viral Pathogenesis and Replication

  • Chapter
  • First Online:
Book cover Viruses and Human Cancer

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 193))

Abstract

Human herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV), is the second identified human gammaherpesvirus. Like its relative Epstein-Barr virus, HHV-8 is linked to B-cell tumors, specifically primary effusion lymphoma and multicentric Castleman’s disease, in addition to endothelial-derived KS. HHV-8 is unusual in its possession of a plethora of “accessory” genes and encoded proteins in addition to the core, conserved herpesvirus and gammaherpesvirus genes that are necessary for basic biological functions of these viruses. The HHV-8 accessory proteins specify not only activities deducible from their cellular protein homologies but also novel, unsuspected activities that have revealed new mechanisms of virus–host interaction that serve virus replication or latency and may contribute to the development and progression of virus-associated neoplasia. These proteins include viral interleukin-6 (vIL-6), viral chemokines (vCCLs), viral G protein–coupled receptor (vGPCR), viral interferon regulatory factors (vIRFs), and viral antiapoptotic proteins homologous to FLICE (FADD-like IL-1β converting enzyme)-inhibitory protein (FLIP) and survivin. Other HHV-8 proteins, such as signaling membrane receptors encoded by open reading frames K1 and K15, also interact with host mechanisms in unique ways and have been implicated in viral pathogenesis. Additionally, a set of micro-RNAs encoded by HHV-8 appear to modulate expression of multiple host proteins to provide conditions conducive to virus persistence within the host and could also contribute to HHV-8-induced neoplasia. Here, we review the molecular biology underlying these novel virus–host interactions and their potential roles in both virus biology and virus-associated disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abend JR, Uldrick T, Ziegelbauer JM (2010) Regulation of tumor necrosis factor-like weak inducer of apoptosis receptor protein (TWEAKR) expression by Kaposi’s sarcoma-associated herpesvirus microRNA prevents TWEAK-induced apoptosis and inflammatory cytokine expression. J Virol 84:12139–12151

    Article  PubMed  CAS  Google Scholar 

  • Albrecht JC, Nicholas J, Cameron KR, Newman C, Fleckenstein B, Honess RW (1992) Herpesvirus saimiri has a gene specifying a homologue of the cellular membrane glycoprotein CD59. Virology 190:527–530

    Article  PubMed  CAS  Google Scholar 

  • Alexander L, Denekamp L, Knapp A, Auerbach MR, Damania B, Desrosiers RC (2000) The primary sequence of rhesus monkey rhadinovirus isolate 26–95: sequence similarities to Kaposi’s sarcoma-associated herpesvirus and rhesus monkey rhadinovirus isolate 17577. J Virol 74:3388–3398

    Article  PubMed  CAS  Google Scholar 

  • Ambrosini G, Adida C, Altieri DC (1997) A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3:917–921

    Article  PubMed  CAS  Google Scholar 

  • An FQ, Compitello N, Horwitz E, Sramkoski M, Knudsen ES, Renne R (2005) The latency-associated nuclear antigen of Kaposi’s sarcoma-associated herpesvirus modulates cellular gene expression and protects lymphoid cells from p16 INK4A-induced cell cycle arrest. J Biol Chem 280:3862–3874

    Article  PubMed  CAS  Google Scholar 

  • An J, Sun Y, Sun R, Rettig MB (2003) Kaposi’s sarcoma-associated herpesvirus encoded vFLIP induces cellular IL-6 expression: the role of the NF-kappaB and JNK/AP1 pathways. Oncogene 22:3371–3385

    Article  PubMed  CAS  Google Scholar 

  • Angell JE, Lindner DJ, Shapiro PS, Hofmann ER, Kalvakolanu DV (2000) Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach. J Biol Chem 275:33416–33426

    Article  PubMed  CAS  Google Scholar 

  • Aoki Y, Feldman GM, Tosato G (2003) Inhibition of STAT3 signaling induces apoptosis and decreases survivin expression in primary effusion lymphoma. Blood 101:1535–1542

    Article  PubMed  CAS  Google Scholar 

  • Aoki Y, Jaffe ES, Chang Y, Jones K, Teruya-Feldstein J, Moore PS, Tosato G (1999) Angiogenesis and hematopoiesis induced by Kaposi’s sarcoma-associated herpesvirus-encoded interleukin-6. Blood 93:4034–4043

    PubMed  CAS  Google Scholar 

  • Aoki Y, Narazaki M, Kishimoto T, Tosato G (2001) Receptor engagement by viral interleukin-6 encoded by Kaposi sarcoma-associated herpesvirus. Blood 98:3042–3049

    Article  PubMed  CAS  Google Scholar 

  • Aoki Y, Tosato G (1999) Role of vascular endothelial growth factor/vascular permeability factor in the pathogenesis of Kaposi’s sarcoma-associated herpesvirus-infected primary effusion lymphomas. Blood 94:4247–4254

    PubMed  CAS  Google Scholar 

  • Aoki Y, Tosato G (2003) Targeted inhibition of angiogenic factors in AIDS-related disorders. Curr Drug Targets Infect Disord 3:115–128

    Article  PubMed  CAS  Google Scholar 

  • Areste C, Mutocheluh M, Blackbourn DJ (2009) Identification of caspase-mediated decay of interferon regulatory factor-3, exploited by a Kaposi sarcoma-associated herpesvirus immunoregulatory protein. J Biol Chem 284:23272–23285

    Article  PubMed  CAS  Google Scholar 

  • Arvanitakis L, Mesri EA, Nador RG, Said JW, Asch AS, Knowles DM, Cesarman E (1996) Establishment and characterization of a primary effusion (body cavity-based) lymphoma cell line (BC-3) harboring kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8) in the absence of Epstein-Barr virus. Blood 88:2648–2654

    PubMed  CAS  Google Scholar 

  • Bais C, Santomasso B, Coso O, Arvanitakis L, Raaka EG, Gutkind JS, Asch AS, Cesarman E, Gershengorn MC, Mesri EA (1998) G-protein-coupled receptor of Kaposi’s sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator. Nature 391:86–89

    Article  PubMed  CAS  Google Scholar 

  • Barbera AJ, Chodaparambil JV, Kelley-Clarke B, Joukov V, Walter JC, Luger K, Kaye KM (2006) The nucleosomal surface as a docking station for Kaposi’s sarcoma herpesvirus LANA. Science 311:856–861

    Article  PubMed  CAS  Google Scholar 

  • Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  PubMed  CAS  Google Scholar 

  • Bartoli M, Gu X, Tsai NT, Venema RC, Brooks SE, Marrero MB, Caldwell RB (2000) Vascular endothelial growth factor activates STAT proteins in aortic endothelial cells. J Biol Chem 275:33189–33192

    Article  PubMed  CAS  Google Scholar 

  • Belanger C, Gravel A, Tomoiu A, Janelle ME, Gosselin J, Tremblay MJ, Flamand L (2001) Human herpesvirus 8 viral FLICE-inhibitory protein inhibits Fas-mediated apoptosis through binding and prevention of procaspase-8 maturation. J Hum Virol 4:62–73

    PubMed  CAS  Google Scholar 

  • Bellare P, Ganem D (2009) Regulation of KSHV lytic switch protein expression by a virus-encoded microRNA: an evolutionary adaptation that fine-tunes lytic reactivation. Cell Host Microbe 6:570–575

    Article  PubMed  CAS  Google Scholar 

  • Bertin J, Armstrong RC, Ottilie S, Martin DA, Wang Y, Banks S, Wang GH, Senkevich TG, Alnemri ES, Moss B, Lenardo MJ, Tomaselli KJ, Cohen JI (1997) Death effector domain-containing herpesvirus and poxvirus proteins inhibit both Fas- and TNFR1-induced apoptosis. Proc Natl Acad Sci U S A 94:1172–1176

    Article  PubMed  CAS  Google Scholar 

  • Boshoff C, Endo Y, Collins PD, Takeuchi Y, Reeves JD, Schweickart VL, Siani MA, Sasaki T, Williams TJ, Gray PW, Moore PS, Chang Y, Weiss RA (1997) Angiogenic and HIV-inhibitory functions of KSHV-encoded chemokines. Science 278:290–294

    Article  PubMed  CAS  Google Scholar 

  • Boulanger MJ, Chow DC, Brevnova EE, Garcia KC (2003) Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex. Science 300:2101–2104

    Article  PubMed  CAS  Google Scholar 

  • Boulanger MJ, Cow DC, Brevnova, EE, Martick M. Sandford G, Nicholas J, Garcia KC (2004) Molecular mechanisms for viral mimicry of a human cytokine: activation of gp130 by HHV-8 interleukin 6. J Mol Biol 335:641–654

    Google Scholar 

  • Bram RJ, Crabtree GR (1994) Calcium signalling in T cells stimulated by a cyclophilin B-binding protein. Nature 371:355–358

    Article  PubMed  CAS  Google Scholar 

  • Brinkmann MM, Glenn M, Rainbow L, Kieser A, Henke-Gendo C, Schulz TF (2003) Activation of mitogen-activated protein kinase and NF-kappaB pathways by a Kaposi’s sarcoma-associated herpesvirus K15 membrane protein. J Virol 77:9346–9358

    Article  PubMed  CAS  Google Scholar 

  • Brinkmann MM, Pietrek M, Dittrich-Breiholz O, Kracht M, Schulz TF (2007) Modulation of host gene expression by the K15 protein of Kaposi’s sarcoma-associated herpesvirus. J Virol 81:42–58

    Article  PubMed  CAS  Google Scholar 

  • Brinkmann MM, Schulz TF (2006) Regulation of intracellular signalling by the terminal membrane proteins of members of the Gammaherpesvirinae. J Gen Virol 87:1047–1074

    Article  PubMed  CAS  Google Scholar 

  • Brown HJ, Song MJ, Deng H, Wu TT, Cheng G, Sun R (2003) NF-kappaB inhibits gammaherpesvirus lytic replication. J Virol 77:8532–8540

    Article  PubMed  CAS  Google Scholar 

  • Bubman D, Guasparri I, Cesarman E (2007) Deregulation of c-Myc in primary effusion lymphoma by Kaposi’s sarcoma herpesvirus latency-associated nuclear antigen. Oncogene 26:4979–4986

    Article  PubMed  CAS  Google Scholar 

  • Burger R, Neipel F, Fleckenstein B, Savino R, Ciliberto G, Kalden JR, Gramatzki M (1998) Human herpesvirus type 8 interleukin-6 homologue is functionally active on human myeloma cells. Blood 91:1858–1863

    PubMed  CAS  Google Scholar 

  • Burger R, Wendler J, Antoni K, Helm G, Kalden JR, Gramatzki M (1994) Interleukin-6 production in B-cell neoplasias and Castleman’s disease: evidence for an additional paracrine loop. Ann Hematol 69:25–31

    Article  PubMed  CAS  Google Scholar 

  • Burysek L, Pitha PM (2001) Latently expressed human herpesvirus 8-encoded interferon regulatory factor 2 inhibits double-stranded RNA-activated protein kinase. J Virol 75:2345–2352

    Article  PubMed  CAS  Google Scholar 

  • Burysek L, Yeow WS, Lubyova B, Kellum M, Schafer SL, Huang YQ, Pitha PM (1999a) Functional analysis of human herpesvirus 8-encoded viral interferon regulatory factor 1 and its association with cellular interferon regulatory factors and p300. J Virol 73:7334–7342

    PubMed  CAS  Google Scholar 

  • Burysek L, Yeow WS, Pitha PM (1999b) Unique properties of a second human herpesvirus 8-encoded interferon regulatory factor (vIRF-2). J Hum Virol 2:19–32

    PubMed  CAS  Google Scholar 

  • Cai X, Lu S, Zhang Z, Gonzalez CM, Damania B, Cullen BR (2005) Kaposi’s sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells. Proc Natl Acad Sci U S A 102:5570–5575

    Article  PubMed  CAS  Google Scholar 

  • Cannon M (2007) The KSHV and other human herpesviral G protein-coupled receptors. Curr Top Microbiol Immunol 312:137–156

    Article  PubMed  CAS  Google Scholar 

  • Cannon M, Philpott NJ, Cesarman E (2003) The Kaposi’s sarcoma-associated herpesvirus G protein-coupled receptor has broad signaling effects in primary effusion lymphoma cells. J Virol 77:57–67

    Article  PubMed  CAS  Google Scholar 

  • Carbone A, Cilia AM, Gloghini A, Capello D, Perin T, Bontempo D, Canzonieri V, Tirelli U, Volpe R, Gaidano G (2000) Primary effusion lymphoma cell lines harbouring human herpesvirus type-8. Leuk Lymphoma 36:447–456

    Article  PubMed  CAS  Google Scholar 

  • Caselli E, Fiorentini S, Amici C, Di Luca D, Caruso A, Santoro MG (2007) Human herpesvirus 8 acute infection of endothelial cells induces monocyte chemoattractant protein 1-dependent capillary-like structure formation: role of the IKK/NF-kappaB pathway. Blood 109:2718–2726

    PubMed  CAS  Google Scholar 

  • Chandriani S, Ganem D (2010) Array-based transcript profiling and limiting-dilution reverse transcription-PCR analysis identify additional latent genes in Kaposi’s sarcoma-associated herpesvirus. J Virol 84:5565–5573

    Article  PubMed  CAS  Google Scholar 

  • Chang Y, Moore PS (1996) Kaposi’s Sarcoma (KS)-associated herpesvirus and its role in KS. Infect Agents Dis 5:215–222

    PubMed  CAS  Google Scholar 

  • Chaudhary PM, Jasmin A, Eby MT, Hood L (1999) Modulation of the NF-kappa B pathway by virally encoded death effector domains-containing proteins. Oncogene 18:5738–5746

    Article  PubMed  CAS  Google Scholar 

  • Chen D, Cousins E, Sandford G, Nicholas J (2012) Human herpesvirus 8 viral interleukin-6 interacts with splice variant 2 of vitamin K epoxide reductase complex subunit 1. J Virol 86:1577–1588

    Article  PubMed  CAS  Google Scholar 

  • Chen D, Nicholas J (2006) Structural requirements for gp80 independence of human herpesvirus 8 interleukin-6 (vIL-6) and evidence for gp80 stabilization of gp130 signaling complexes induced by vIL-6. J Virol 80:9811–9821

    Article  PubMed  CAS  Google Scholar 

  • Chen D, Sandford G, Nicholas J (2009a) Intracellular signaling mechanisms and activities of human herpesvirus 8 interleukin-6. J Virol 83:722–733

    Article  PubMed  CAS  Google Scholar 

  • Chen S, Bacon KB, Li L, Garcia GE, Xia Y, Lo D, Thompson DA, Siani MA, Yamamoto T, Harrison JK, Feng L (1998) In vivo inhibition of CC and CX3C chemokine-induced leukocyte infiltration and attenuation of glomerulonephritis in Wistar-Kyoto (WKY) rats by vMIP-II. J Exp Med 188:193–198

    Article  PubMed  CAS  Google Scholar 

  • Chen W, Hilton IB, Staudt MR, Burd CE, Dittmer DP (2010) Distinct p53, p53:LANA, and LANA complexes in Kaposi’s Sarcoma–associated Herpesvirus Lymphomas. J Virol 84:3898–3908

    Article  PubMed  CAS  Google Scholar 

  • Chen X, Cheng L, Jia X, Zeng Y, Yao S, Lv Z, Qin D, Fang X, Lei Y, Lu C (2009b) Human immunodeficiency virus type 1 Tat accelerates Kaposi sarcoma-associated herpesvirus Kaposin A-mediated tumorigenesis of transformed fibroblasts in vitro as well as in nude and immunocompetent mice. Neoplasia 11:1272–1284

    PubMed  CAS  Google Scholar 

  • Choi JK, Lee BS, Shim SN, Li M, Jung JU (2000) Identification of the novel K15 gene at the rightmost end of the Kaposi’s sarcoma-associated herpesvirus genome. J Virol 74:436–446

    Article  PubMed  CAS  Google Scholar 

  • Choi YB, Nicholas J (2008) Autocrine and paracrine promotion of cell survival and virus replication by human herpesvirus 8 chemokines. J Virol 82:6501–6513

    Article  PubMed  CAS  Google Scholar 

  • Choi YB, Nicholas J (2010) Bim nuclear translocation and inactivation by viral interferon regulatory factor. PLoS Pathog 6:e1001031

    Article  PubMed  CAS  Google Scholar 

  • Choi YB, Sandford G, Nicholas J (2012) Human herpesvirus 8 interferon regulatory factor-mediated BH3-only protein Inhibition via Bid BH3-B mimicry. PLoS Pathog 8(6):e1002748

    Google Scholar 

  • Chow D, He X, Snow AL, Rose-John S, Garcia KC (2001) Structure of an extracellular gp130 cytokine receptor signaling complex. Science 291:2150–2155

    Article  PubMed  CAS  Google Scholar 

  • Chugh P, Matta H, Schamus S, Zachariah S, Kumar A, Richardson JA, Smith AL, Chaudhary PM (2005) Constitutive NF-kappaB activation, normal Fas-induced apoptosis, and increased incidence of lymphoma in human herpes virus 8 K13 transgenic mice. Proc Natl Acad Sci U S A 102:12885–12890

    Article  PubMed  CAS  Google Scholar 

  • Couty JP, Geras-Raaka E, Weksler BB, Gershengorn MC (2001) Kaposi’s sarcoma-associated herpesvirus G protein-coupled receptor signals through multiple pathways in endothelial cells. J Biol Chem 276:33805–33811

    Article  PubMed  CAS  Google Scholar 

  • Crump MP, Elisseeva E, Gong J, Clark-Lewis I, Sykes BD (2001) Structure/function of human herpesvirus-8 MIP-II (1–71) and the antagonist N-terminal segment (1–10). FEBS Lett 489:171–175

    Article  PubMed  CAS  Google Scholar 

  • Cunningham C, Barnard S, Blackbourn DJ, Davison AJ (2003) Transcription mapping of human herpesvirus 8 genes encoding viral interferon regulatory factors. J Gen Virol 84:1471–1483

    Article  PubMed  CAS  Google Scholar 

  • Dairaghi DJ, Fan RA, McMaster BE, Hanley MR, Schall TJ (1999) HHV8-encoded vMIP-I selectively engages chemokine receptor CCR8. Agonist and antagonist profiles of viral chemokines. J Biol Chem 274:21569–21574

    Article  PubMed  CAS  Google Scholar 

  • Damania B, Li M, Choi JK, Alexander L, Jung JU, Desrosiers RC (1999) Identification of the R1 oncogene and its protein product from the rhadinovirus of rhesus monkeys. J Virol 73:5123–5131

    PubMed  CAS  Google Scholar 

  • Dittmer DP (2003) Transcription profile of Kaposi’s sarcoma-associated herpesvirus in primary Kaposi’s sarcoma lesions as determined by real-time PCR arrays. Cancer Res 63:2010–2015

    PubMed  CAS  Google Scholar 

  • Djerbi M, Screpanti V, Catrina AI, Bogen B, Biberfeld P, Grandien A (1999) The inhibitor of death receptor signaling, FLICE-inhibitory protein defines a new class of tumor progression factors. J Exp Med 190:1025–1032

    Article  PubMed  CAS  Google Scholar 

  • Dolken L, Malterer G, Erhard F, Kothe S, Friedel CC, Suffert G, Marcinowski L, Motsch N, Barth S, Beitzinger M, Lieber D, Bailer SM, Hoffmann R, Ruzsics Z, Kremmer E, Pfeffer S, Zimmer R, Koszinowski UH, Grasser F, Meister G, Haas J (2010) Systematic analysis of viral and cellular microRNA targets in cells latently infected with human gamma-herpesviruses by RISC immunoprecipitation assay. Cell Host Microbe 7:324–334

    Article  PubMed  CAS  Google Scholar 

  • Ensoli B, Sgadari C, Barillari G, Sirianni MC, Sturzl M, Monini P (2001) Biology of Kaposi’s sarcoma. Eur J Cancer 37:1251–1269

    Article  PubMed  CAS  Google Scholar 

  • Ensoli B, Sturzl M (1998) Kaposi’s sarcoma: a result of the interplay among inflammatory cytokines, angiogenic factors and viral agents. Cytokine Growth Factor Rev 9:63–83

    Article  PubMed  CAS  Google Scholar 

  • Esteban M, Garcia MA, Domingo-Gil E, Arroyo J, Nombela C, Rivas C (2003) The latency protein LANA2 from Kaposi’s sarcoma-associated herpesvirus inhibits apoptosis induced by dsRNA-activated protein kinase but not RNase L activation. J Gen Virol 84:1463–1470

    Article  PubMed  CAS  Google Scholar 

  • Feng P, Park J, Lee BS, Lee SH, Bram RJ, Jung JU (2002) Kaposi’s sarcoma-associated herpesvirus mitochondrial K7 protein targets a cellular calcium-modulating cyclophilin ligand to modulate intracellular calcium concentration and inhibit apoptosis. J Virol 76:11491–11504

    Article  PubMed  CAS  Google Scholar 

  • Feng P, Scott CW, Cho NH, Nakamura H, Chung YH, Monteiro MJ, Jung JU (2004) Kaposi’s sarcoma-associated herpesvirus K7 protein targets a ubiquitin-like/ubiquitin-associated domain-containing protein to promote protein degradation. Mol Cell Biol 24:3938–3948

    Article  PubMed  CAS  Google Scholar 

  • Field N, Low W, Daniels M, Howell S, Daviet L, Boshoff C, Collins M (2003) KSHV vFLIP binds to IKK-gamma to activate IKK. J Cell Sci 116:3721–3728

    Article  PubMed  CAS  Google Scholar 

  • Fielding CA, McLoughlin RM, Colmont CS, Kovaleva M, Harris DA, Rose-John S, Topley N, Jones SA (2005) Viral IL-6 blocks neutrophil infiltration during acute inflammation. J Immunol 175:4024–4029

    PubMed  CAS  Google Scholar 

  • Friborg J Jr, Kong W, Hottiger MO, Nabel GJ (1999) p53 inhibition by the LANA protein of KSHV protects against cell death. Nature 402:889–894

    PubMed  CAS  Google Scholar 

  • Fujimuro M, Hayward SD (2003) The latency-associated nuclear antigen of Kaposi’s sarcoma-associated herpesvirus manipulates the activity of glycogen synthase kinase-3beta. J Virol 77:8019–8030

    Article  PubMed  CAS  Google Scholar 

  • Fujimuro M, Wu FY, ApRhys C, Kajumbula H, Young DB, Hayward GS, Hayward SD (2003) A novel viral mechanism for dysregulation of beta-catenin in Kaposi’s sarcoma-associated herpesvirus latency. Nat Med 9:300–306

    Article  PubMed  CAS  Google Scholar 

  • Fuld S, Cunningham C, Klucher K, Davison AJ, Blackbourn DJ (2006) Inhibition of interferon signaling by the Kaposi’s sarcoma-associated herpesvirus full-length viral interferon regulatory factor 2 protein. J Virol 80:3092–3097

    Article  PubMed  CAS  Google Scholar 

  • Gaidano G, Pastore C, Gloghini A, Volpe G, Capello D, Polito P, Vaccher E, Tirelli U, Saglio G, Carbone A (1997) Human herpesvirus type-8 (HHV-8) in haematopoietic neoplasia. Leuk Lymphoma 24:257–266

    PubMed  CAS  Google Scholar 

  • Glas R, Franksson L, Une C, Eloranta ML, Ohlen C, Orn A, Karre K (2000) Recruitment and activation of natural killer (NK) cells in vivo determined by the target cell phenotype. An adaptive component of NK cell-mediated responses. J Exp Med 191:129–138

    Article  PubMed  CAS  Google Scholar 

  • Glenn M, Rainbow L, Aurade F, Davison A, Schulz TF (1999) Identification of a spliced gene from Kaposi’s sarcoma-associated herpesvirus encoding a protein with similarities to latent membrane proteins 1 and 2A of Epstein-Barr virus. J Virol 73:6953–6963

    PubMed  CAS  Google Scholar 

  • Godfrey A, Anderson J, Papanastasiou A, Takeuchi Y, Boshoff C (2005) Inhibiting primary effusion lymphoma by lentiviral vectors encoding short hairpin RNA. Blood 105:2510–2518

    Article  PubMed  CAS  Google Scholar 

  • Gottwein E, Corcoran DL, Mukherjee N, Skalsky RL, Hafner M, Nusbaum JD, Shamulailatpam P, Love CL, Dave SS, Tuschl T, Ohler U, Cullen BR (2011) Viral microRNA targetome of KSHV-infected primary effusion lymphoma cell lines. Cell Host Microbe 10:515–526

    Article  PubMed  CAS  Google Scholar 

  • Gottwein E, Cullen BR (2010) A human herpesvirus microRNA inhibits p21 expression and attenuates p21-mediated cell cycle arrest. J Virol 84:5229–5237

    Article  PubMed  CAS  Google Scholar 

  • Gottwein E, Mukherjee N, Sachse C, Frenzel C, Majoros WH, Chi JT, Braich R, Manoharan M, Soutschek J, Ohler U, Cullen BR (2007) A viral microRNA functions as an orthologue of cellular miR-155. Nature 450:1096–1099

    Article  PubMed  CAS  Google Scholar 

  • Grossmann C, Ganem D (2008) Effects of NFkappaB activation on KSHV latency and lytic reactivation are complex and context-dependent. Virology 375:94–102

    Article  PubMed  CAS  Google Scholar 

  • Grossmann C, Podgrabinska S, Skobe M, Ganem D (2006) Activation of NF-kappaB by the latent vFLIP gene of Kaposi’s sarcoma-associated herpesvirus is required for the spindle shape of virus-infected endothelial cells and contributes to their proinflammatory phenotype. J Virol 80:7179–7185

    Article  PubMed  CAS  Google Scholar 

  • Guasparri I, Keller SA, Cesarman E (2004) KSHV vFLIP is essential for the survival of infected lymphoma cells. J Exp Med 199:993–1003

    Article  PubMed  CAS  Google Scholar 

  • Guasparri I, Wu H, Cesarman E (2006) The KSHV oncoprotein vFLIP contains a TRAF-interacting motif and requires TRAF2 and TRAF3 for signalling. EMBO Rep 7:114–119

    Article  PubMed  CAS  Google Scholar 

  • Haddad L, El Hajj H, Abou-Merhi R, Kfoury Y, Mahieux R, El-Sabban M, Bazarbachi A (2008) KSHV-transformed primary effusion lymphoma cells induce a VEGF-dependent angiogenesis and establish functional gap junctions with endothelial cells. Leukemia 22:826–834

    Article  PubMed  CAS  Google Scholar 

  • Hansen A, Henderson S, Lagos D, Nikitenko L, Coulter E, Roberts S, Gratrix F, Plaisance K, Renne R, Bower M, Kellam P, Boshoff C (2010) KSHV-encoded miRNAs target MAF to induce endothelial cell reprogramming. Genes Dev 24:195–205

    Article  PubMed  CAS  Google Scholar 

  • Hayward GS, Zong JC (2007) Modern evolutionary history of the human KSHV genome. Curr Top Microbiol Immunol 312:1–42

    Article  PubMed  CAS  Google Scholar 

  • Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G, Schaper F (2003) Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 374:1–20

    Article  PubMed  CAS  Google Scholar 

  • Heinrich PC, Behrmann I, Muller-Newen G, Schaper F, Graeve L (1998) Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J 334(Pt 2):297–314

    PubMed  CAS  Google Scholar 

  • Heinzelmann K, Scholz BA, Nowak A, Fossum E, Kremmer E, Haas J, Frank R, Kempkes B (2010) Kaposi’s sarcoma-associated herpesvirus viral interferon regulatory factor 4 (vIRF4/K10) is a novel interaction partner of CSL/CBF1, the major downstream effector of Notch signaling. J Virol 84:12255–12264

    Article  PubMed  CAS  Google Scholar 

  • Hu S, Vincenz C, Buller M, Dixit VM (1997) A novel family of viral death effector domain-containing molecules that inhibit both CD-95- and tumor necrosis factor receptor-1-induced apoptosis. J Biol Chem 272:9621–9624

    Article  PubMed  CAS  Google Scholar 

  • Ishiyama T, Nakamura S, Akimoto Y, Koike M, Tomoyasu S, Tsuruoka N, Murata Y, Sato T, Wakabayashi Y, Chiba S (1994) Immunodeficiency and IL-6 production by peripheral blood monocytes in multicentric Castleman’s disease. Br J Haematol 86:483–489

    Article  PubMed  CAS  Google Scholar 

  • Jenner RG, Alba MM, Boshoff C, Kellam P (2001) Kaposi’s sarcoma-associated herpesvirus latent and lytic gene expression as revealed by DNA arrays. J Virol 75:891–902

    Article  PubMed  CAS  Google Scholar 

  • Jones KD, Aoki Y, Chang Y, Moore PS, Yarchoan R, Tosato G (1999) Involvement of interleukin-10 (IL-10) and viral IL-6 in the spontaneous growth of Kaposi’s sarcoma herpesvirus-associated infected primary effusion lymphoma cells. Blood 94:2871–2879

    PubMed  CAS  Google Scholar 

  • Joo CH, Shin YC, Gack M, Wu L, Levy D, Jung JU (2007) Inhibition of interferon regulatory factor 7 (IRF7)-mediated interferon signal transduction by the Kaposi’s sarcoma-associated herpesvirus viral IRF homolog vIRF3. J Virol 81:8282–8292

    Article  PubMed  CAS  Google Scholar 

  • Karim R, Tse G, Putti T, Scolyer R, Lee S (2004) The significance of the Wnt pathway in the pathology of human cancers. Pathology 36:120–128

    Article  PubMed  CAS  Google Scholar 

  • Kawa K (2000) Epstein-Barr virus–associated diseases in humans. Int J Hematol 71:108–117

    PubMed  CAS  Google Scholar 

  • Kaye KM, Izumi KM, Kieff E (1993) Epstein-Barr virus latent membrane protein 1 is essential for B-lymphocyte growth transformation. Proc Natl Acad Sci U S A 90:9150–9154

    Article  PubMed  CAS  Google Scholar 

  • Keller SA, Schattner EJ, Cesarman E (2000) Inhibition of NF-kappaB induces apoptosis of KSHV-infected primary effusion lymphoma cells. Blood 96:2537–2542

    PubMed  CAS  Google Scholar 

  • Kishimoto T, Akira S, Narazaki M, Taga T (1995) Interleukin-6 family of cytokines and gp130. Blood 86:1243–1254

    PubMed  CAS  Google Scholar 

  • Kledal TN, Rosenkilde MM, Coulin F, Simmons G, Johnsen AH, Alouani S, Power CA, Luttichau HR, Gerstoft J, Clapham PR, Clark-Lewis I, Wells TN, Schwartz TW (1997) A broad-spectrum chemokine antagonist encoded by Kaposi’s sarcoma-associated herpesvirus. Science 277:1656–1659

    Article  PubMed  CAS  Google Scholar 

  • Kleijnen MF, Shih AH, Zhou P, Kumar S, Soccio RE, Kedersha NL, Gill G, Howley PM (2000) The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome. Mol Cell 6:409–419

    Article  PubMed  CAS  Google Scholar 

  • Kliche S, Nagel W, Kremmer E, Atzler C, Ege A, Knorr T, Koszinowski U, Kolanus W, Haas J (2001) Signaling by human herpesvirus 8 kaposin A through direct membrane recruitment of cytohesin-1. Mol Cell 7:833–843

    Article  PubMed  CAS  Google Scholar 

  • Kovaleva M, Bussmeyer I, Rabe B, Grotzinger J, Sudarman E, Eichler J, Conrad U, Rose-John S, Scheller J (2006) Abrogation of viral interleukin-6 (vIL-6)-induced signaling by intracellular retention and neutralization of vIL-6 with an anti-vIL-6 single-chain antibody selected by phage display. J Virol 80:8510–8520

    Article  PubMed  CAS  Google Scholar 

  • Krithivas A, Young DB, Liao G, Greene D, Hayward SD (2000) Human herpesvirus 8 LANA interacts with proteins of the mSin3 corepressor complex and negatively regulates Epstein-Barr virus gene expression in dually infected PEL cells. J Virol 74:9637–9645

    Article  PubMed  CAS  Google Scholar 

  • Kuwana T, Bouchier-Hayes L, Chipuk JE, Bonzon C, Sullivan BA, Green DR, Newmeyer DD (2005) BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. Mol Cell 17:525–535

    Article  PubMed  CAS  Google Scholar 

  • Lagunoff M, Ganem D (1997) The structure and coding organization of the genomic termini of Kaposi’s sarcoma-associated herpesvirus. Virology 236:147–154

    Article  PubMed  CAS  Google Scholar 

  • Lagunoff M, Lukac DM, Ganem D (2001) Immunoreceptor tyrosine-based activation motif-dependent signaling by Kaposi’s sarcoma-associated herpesvirus K1 protein: effects on lytic viral replication. J Virol 75:5891–5898

    Article  PubMed  CAS  Google Scholar 

  • Lee BS, Connole M, Tang Z, Harris NL, Jung JU (2003a) Structural analysis of the Kaposi’s sarcoma-associated herpesvirus K1 protein. J Virol 77:8072–8086

    Article  PubMed  CAS  Google Scholar 

  • Lee BS, Lee SH, Feng P, Chang H, Cho NH, Jung JU (2005) Characterization of the Kaposi’s sarcoma-associated herpesvirus K1 signalosome. J Virol 79:12173–12184

    Article  PubMed  CAS  Google Scholar 

  • Lee H, Guo J, Li M, Choi JK, DeMaria M, Rosenzweig M, Jung JU (1998a) Identification of an immunoreceptor tyrosine-based activation motif of K1 transforming protein of Kaposi’s sarcoma-associated herpesvirus. Mol Cell Biol 18:5219–5228

    PubMed  CAS  Google Scholar 

  • Lee H, Veazey R, Williams K, Li M, Guo J, Neipel F, Fleckenstein B, Lackner A, Desrosiers RC, Jung JU (1998b) Deregulation of cell growth by the K1 gene of Kaposi’s sarcoma-associated herpesvirus. Nat Med 4:435–440

    Article  PubMed  CAS  Google Scholar 

  • Lee HR, Choi WC, Lee S, Hwang J, Hwang E, Guchhait K, Haas J, Toth Z, Jeon YH, Oh TK, Kim MH, Jung JU (2011) Bilateral inhibition of HAUSP deubiquitinase by a viral interferon regulatory factor protein. Nat Struct Mol Biol 18:1336–1344

    Article  PubMed  CAS  Google Scholar 

  • Lee HR, Kim MH, Lee JS, Liang C, Jung JU (2009a) Viral interferon regulatory factors. J Interferon Cytokine Res 29:621–627

    Article  PubMed  CAS  Google Scholar 

  • Lee HR, Toth Z, Shin YC, Lee JS, Chang H, Gu W, Oh TK, Kim MH, Jung JU (2009b) Kaposi’s sarcoma-associated herpesvirus viral interferon regulatory factor 4 targets MDM2 to deregulate the p53 tumor suppressor pathway. J Virol 83:6739–6747

    Article  PubMed  CAS  Google Scholar 

  • Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Radmark O, Kim S, Kim VN (2003b) The nuclear RNase III Drosha initiates microRNA processing. Nature 425:415–419

    Article  PubMed  CAS  Google Scholar 

  • Lei X, Bai Z, Ye F, Xie J, Kim CG, Huang Y, Gao SJ (2010) Regulation of NF-kappaB inhibitor IkappaBalpha and viral replication by a KSHV microRNA. Nat Cell Biol 12:193–199

    Article  PubMed  CAS  Google Scholar 

  • Li H, Komatsu T, Dezube BJ, Kaye KM (2002) The Kaposi’s sarcoma-associated herpesvirus K12 transcript from a primary effusion lymphoma contains complex repeat elements, is spliced, and initiates from a novel promoter. J Virol 76:11880–11888

    Article  PubMed  CAS  Google Scholar 

  • Li M, Damania B, Alvarez X, Ogryzko V, Ozato K, Jung JU (2000) Inhibition of p300 histone acetyltransferase by viral interferon regulatory factor. Mol Cell Biol 20:8254–8263

    Article  PubMed  CAS  Google Scholar 

  • Liang D, Lin X, Lan K (2012) Looking at Kaposi’s Sarcoma-Associated Herpesvirus-Host Interactions from a microRNA Viewpoint. Front Microbiol 2:271

    Article  PubMed  CAS  Google Scholar 

  • Lim CS, Seet BT, Ingham RJ, Gish G, Matskova L, Winberg G, Ernberg I, Pawson T (2007) The K15 protein of Kaposi’s sarcoma-associated herpesvirus recruits the endocytic regulator intersectin 2 through a selective SH3 domain interaction. Biochemistry 46:9874–9885

    Article  PubMed  CAS  Google Scholar 

  • Lin CW, Tu PF, Hsiao NW, Chang CY, Wan L, Lin YT, Chang HW (2007) Identification of a novel septin 4 protein binding to human herpesvirus 8 kaposin A protein using a phage display cDNA library. J Virol Methods 143:65–72

    Article  PubMed  CAS  Google Scholar 

  • Lin R, Genin P, Mamane Y, Sgarbanti M, Battistini A, Harrington WJ Jr, Barber GN, Hiscott J (2001) HHV-8 encoded vIRF-1 represses the interferon antiviral response by blocking IRF-3 recruitment of the CBP/p300 coactivators. Oncogene 20:800–811

    Article  PubMed  CAS  Google Scholar 

  • Lin X, Liang D, He Z, Deng Q, Robertson ES, Lan K (2011) miR-K12-7-5p encoded by Kaposi’s sarcoma-associated herpesvirus stabilizes the latent state by targeting viral ORF50/RTA. PLoS One 6:e16224

    Article  PubMed  CAS  Google Scholar 

  • Lindner SE, Sugden B (2007) The plasmid replicon of Epstein-Barr virus: mechanistic insights into efficient, licensed, extrachromosomal replication in human cells. Plasmid 58:1–12

    Article  PubMed  CAS  Google Scholar 

  • Liu C, Okruzhnov Y, Li H, Nicholas J (2001) Human herpesvirus 8 (HHV-8)-encoded cytokines induce expression of and autocrine signaling by vascular endothelial growth factor (VEGF) in HHV-8-infected primary-effusion lymphoma cell lines and mediate VEGF-independent antiapoptotic effects. J Virol 75:10933–10940

    Article  PubMed  CAS  Google Scholar 

  • Liu C, Sandford G, Fei G, Nicholas J (2004) Galpha protein selectivity determinant specified by a viral chemokine receptor-conserved region in the C tail of the human herpesvirus 8 g protein-coupled receptor. J Virol 78:2460–2471

    Article  PubMed  CAS  Google Scholar 

  • Liu J, Martin H, Shamay M, Woodard C, Tang QQ, Hayward SD (2007a) Kaposi’s sarcoma-associated herpesvirus LANA protein downregulates nuclear glycogen synthase kinase 3 activity and consequently blocks differentiation. J Virol 81:4722–4731

    Article  PubMed  CAS  Google Scholar 

  • Liu J, Martin HJ, Liao G, Hayward SD (2007b) The Kaposi’s sarcoma-associated herpesvirus LANA protein stabilizes and activates c-Myc. J Virol 81:10451–10459

    Article  PubMed  CAS  Google Scholar 

  • Liu L, Eby MT, Rathore N, Sinha SK, Kumar A, Chaudhary PM (2002) The human herpes virus 8-encoded viral FLICE inhibitory protein physically associates with and persistently activates the Ikappa B kinase complex. J Biol Chem 277:13745–13751

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Sun R, Lin X, Liang D, Deng Q, Lan K (2012) Kaposi’s sarcoma-associated herpesvirus-encoded microRNA miR-K12-11 attenuates transforming growth factor beta signaling through suppression of SMAD5. J Virol 86:1372–1381

    Article  PubMed  CAS  Google Scholar 

  • Louahed J, Struyf S, Demoulin JB, Parmentier M, Van Snick J, Van Damme J, Renauld JC (2003) CCR8-dependent activation of the RAS/MAPK pathway mediates anti-apoptotic activity of I-309/ CCL1 and vMIP-I. Eur J Immunol 33:494–501

    Article  PubMed  CAS  Google Scholar 

  • Lu CC, Li Z, Chu CY, Feng J, Sun R, Rana TM (2010a) MicroRNAs encoded by Kaposi’s sarcoma-associated herpesvirus regulate viral life cycle. EMBO Rep 11:784–790

    Article  PubMed  CAS  Google Scholar 

  • Lu F, Stedman W, Yousef M, Renne R, Lieberman PM (2010b) Epigenetic regulation of Kaposi’s sarcoma-associated herpesvirus latency by virus-encoded microRNAs that target Rta and the cellular Rbl2-DNMT pathway. J Virol 84:2697–2706

    Article  PubMed  CAS  Google Scholar 

  • Lubyova B, Kellum MJ, Frisancho JA, Pitha PM (2007) Stimulation of c-Myc transcriptional activity by vIRF-3 of Kaposi sarcoma-associated herpesvirus. J Biol Chem 282:31944–31953

    Article  PubMed  CAS  Google Scholar 

  • Lubyova B, Pitha PM (2000) Characterization of a novel human herpesvirus 8-encoded protein, vIRF-3, that shows homology to viral and cellular interferon regulatory factors. J Virol 74:8194–8201

    Article  PubMed  CAS  Google Scholar 

  • Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U (2004) Nuclear export of microRNA precursors. Science 303:95–98

    Article  PubMed  CAS  Google Scholar 

  • Luttichau HR (2008) The herpesvirus 8 encoded chemokines vCCL2 (vMIP-II) and vCCL3 (vMIP-III) target the human but not the murine lymphotactin receptor. Virol J 5:50

    Article  PubMed  CAS  Google Scholar 

  • Luttichau HR, Johnsen AH, Jurlander J, Rosenkilde MM, Schwartz TW (2007) Kaposi sarcoma-associated herpes virus targets the lymphotactin receptor with both a broad spectrum antagonist vCCL2 and a highly selective and potent agonist vCCL3. J Biol Chem 282:17794–17805

    Article  PubMed  CAS  Google Scholar 

  • Luttichau HR, Lewis IC, Gerstoft J, Schwartz TW (2001) The herpesvirus 8-encoded chemokine vMIP-II, but not the poxvirus-encoded chemokine MC148, inhibits the CCR10 receptor. Eur J Immunol 31:1217–1220

    Article  PubMed  CAS  Google Scholar 

  • Ma X, Kalakonda S, Srinivasula SM, Reddy SP, Platanias LC, Kalvakolanu DV (2007) GRIM-19 associates with the serine protease HtrA2 for promoting cell death. Oncogene 26:4842–4849

    Article  PubMed  CAS  Google Scholar 

  • Mandel-Gutfreund Y, Kosti I, Larisch S (2011) ARTS, the unusual septin: structural and functional aspects. Biol Chem 392:783–790

    Article  PubMed  CAS  Google Scholar 

  • Marcos-Villar L, Lopitz-Otsoa F, Gallego P, Munoz-Fontela C, Gonzalez-Santamaria J, Campagna M, Shou-Jiang G, Rodriguez MS, Rivas C (2009) Kaposi’s sarcoma-associated herpesvirus protein LANA2 disrupts PML oncogenic domains and inhibits PML-mediated transcriptional repression of the survivin gene. J Virol 83:8849–8858

    Article  PubMed  CAS  Google Scholar 

  • Matta H, Chaudhary PM (2004) Activation of alternative NF-kappa B pathway by human herpes virus 8-encoded Fas-associated death domain-like IL-1 beta-converting enzyme inhibitory protein (vFLIP). Proc Natl Acad Sci U S A 101:9399–9404

    Article  PubMed  CAS  Google Scholar 

  • Matta H, Mazzacurati L, Schamus S, Yang T, Sun Q, Chaudhary PM (2007) Kaposi’s sarcoma-associated herpesvirus (KSHV) oncoprotein K13 bypasses TRAFs and directly interacts with the IkappaB kinase complex to selectively activate NF-kappaB without JNK activation. J Biol Chem 282:24858–24865

    Article  PubMed  CAS  Google Scholar 

  • Mbulaiteye S, Marshall V, Bagni RK, Wang CD, Mbisa G, Bakaki PM, Owor AM, Ndugwa CM, Engels EA, Katongole-Mbidde E, Biggar RJ, Whitby D (2006) Molecular evidence for mother-to-child transmission of Kaposi sarcoma-associated herpesvirus in Uganda and K1 gene evolution within the host. J Infect Dis 193:1250–1257

    Article  PubMed  CAS  Google Scholar 

  • McCormick C, Ganem D (2005) The kaposin B protein of KSHV activates the p38/MK2 pathway and stabilizes cytokine mRNAs. Science 307:739–741

    Article  PubMed  CAS  Google Scholar 

  • McCormick C, Ganem D (2006) Phosphorylation and function of the kaposin B direct repeats of Kaposi’s sarcoma-associated herpesvirus. J Virol 80:6165–6170

    Article  PubMed  CAS  Google Scholar 

  • Mesri EA, Cesarman E, Boshoff C (2010) Kaposi’s sarcoma and its associated herpesvirus. Nat Rev Cancer 10:707–719

    Article  PubMed  CAS  Google Scholar 

  • Miles SA, Rezai AR, Salazar-Gonzalez JF, Vander Meyden M, Stevens RH, Logan DM, Mitsuyasu RT, Taga T, Hirano T, Kishimoto T et al (1990) AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6. Proc Natl Acad Sci U S A 87:4068–4072

    Article  PubMed  CAS  Google Scholar 

  • Montaner S, Sodhi A, Molinolo A, Bugge TH, Sawai ET, He Y, Li Y, Ray PE, Gutkind JS (2003) Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi’s sarcomagenesis and can promote the tumorigenic potential of viral latent genes. Cancer Cell 3:23–36

    Article  PubMed  CAS  Google Scholar 

  • Montaner S, Sodhi A, Servitja JM, Ramsdell AK, Barac A, Sawai ET, Gutkind JS (2004) The small GTPase Rac1 links the Kaposi sarcoma-associated herpesvirus vGPCR to cytokine secretion and paracrine neoplasia. Blood 104:2903–2911

    Article  PubMed  CAS  Google Scholar 

  • Moore PS, Boshoff C, Weiss RA, Chang Y (1996) Molecular mimicry of human cytokine and cytokine response pathway genes by KSHV. Science 274:1739–1744

    Article  PubMed  CAS  Google Scholar 

  • Mori Y, Nishimoto N, Ohno M, Inagi R, Dhepakson P, Amou K, Yoshizaki K, Yamanishi K (2000) Human herpesvirus 8-encoded interleukin-6 homologue (viral IL-6) induces endogenous human IL-6 secretion. J Med Virol 61:332–335

    Article  PubMed  CAS  Google Scholar 

  • Munoz-Fontela C, Collado M, Rodriguez E, Garcia MA, Alvarez-Barrientos A, Arroyo J, Nombela C, Rivas C (2005) Identification of a nuclear export signal in the KSHV latent protein LANA2 mediating its export from the nucleus. Exp Cell Res 311:96–105

    Article  PubMed  CAS  Google Scholar 

  • Munoz-Fontela C, Marcos-Villar L, Gallego P, Arroyo J, Da Costa M, Pomeranz KM, Lam EW, Rivas C (2007) Latent protein LANA2 from Kaposi’s sarcoma-associated herpesvirus interacts with 14–3-3 proteins and inhibits FOXO3a transcription factor. J Virol 81:1511–1516

    Article  PubMed  CAS  Google Scholar 

  • Muralidhar S, Pumfery AM, Hassani M, Sadaie MR, Kishishita M, Brady JN, Doniger J, Medveczky P, Rosenthal LJ (1998) Identification of kaposin (open reading frame K12) as a human herpesvirus 8 (Kaposi’s sarcoma-associated herpesvirus) transforming gene. J Virol 72:4980–4988

    PubMed  CAS  Google Scholar 

  • Muralidhar S, Veytsmann G, Chandran B, Ablashi D, Doniger J, Rosenthal LJ (2000) Characterization of the human herpesvirus 8 (Kaposi’s sarcoma-associated herpesvirus) oncogene, kaposin (ORF K12). J Clin Virol 16:203–213

    Article  PubMed  CAS  Google Scholar 

  • Murthy SC, Trimble JJ, Desrosiers RC (1989) Deletion mutants of herpesvirus saimiri define an open reading frame necessary for transformation. J Virol 63:3307–3314

    PubMed  CAS  Google Scholar 

  • Nachmani D, Stern-Ginossar N, Sarid R, Mandelboim O (2009) Diverse herpesvirus microRNAs target the stress-induced immune ligand MICB to escape recognition by natural killer cells. Cell Host Microbe 5:376–385

    Article  PubMed  CAS  Google Scholar 

  • Nakamura H, Li M, Zarycki J, Jung JU (2001) Inhibition of p53 tumor suppressor by viral interferon regulatory factor. J Virol 75:7572–7582

    Article  PubMed  CAS  Google Scholar 

  • Nakamura H, Lu M, Gwack Y, Souvlis J, Zeichner SL, Jung JU (2003) Global changes in Kaposi’s sarcoma-associated virus gene expression patterns following expression of a tetracycline-inducible Rta transactivator. J Virol 77:4205–4220

    Article  PubMed  CAS  Google Scholar 

  • Nakano K, Isegawa Y, Zou P, Tadagaki K, Inagi R, Yamanishi K (2003) Kaposi’s sarcoma-associated herpesvirus (KSHV)-encoded vMIP-I and vMIP-II induce signal transduction and chemotaxis in monocytic cells. Arch Virol 148:871–890

    Article  PubMed  CAS  Google Scholar 

  • Neipel F, Albrecht JC, Ensser A, Huang YQ, Li JJ, Friedman-Kien AE, Fleckenstein B (1997a) Human herpesvirus 8 encodes a homolog of interleukin-6. J Virol 71:839–842

    PubMed  CAS  Google Scholar 

  • Neipel F, Albrecht JC, Fleckenstein B (1997b) Cell-homologous genes in the Kaposi’s sarcoma-associated rhadinovirus human herpesvirus 8: determinants of its pathogenicity? J Virol 71:4187–4192

    PubMed  CAS  Google Scholar 

  • Nicholas J (2005) Human gammaherpesvirus cytokines and chemokine receptors. J Interferon Cytokine Res 25:373–383

    Article  PubMed  CAS  Google Scholar 

  • Nicholas J, Ruvolo VR, Burns WH, Sandford G, Wan X, Ciufo D, Hendrickson SB, Guo HG, Hayward GS, Reitz MS (1997) Kaposi’s sarcoma-associated human herpesvirus-8 encodes homologues of macrophage inflammatory protein-1 and interleukin-6. Nat Med 3:287–292

    Article  PubMed  CAS  Google Scholar 

  • Nicholas J, Zong JC, Alcendor DJ, Ciufo DM, Poole LJ, Sarisky RT, Chiou CJ, Zhang X, Wan X, Guo HG, Reitz MS, Hayward GS (1998) Novel organizational features, captured cellular genes, and strain variability within the genome of KSHV/HHV8. J Natl Cancer Inst Monogr 23:79–88

    Google Scholar 

  • Offermann MK (2007) Kaposi sarcoma herpesvirus-encoded interferon regulator factors. Curr Top Microbiol Immunol 312:185–209

    Article  PubMed  CAS  Google Scholar 

  • Okano M (2000) Haematological associations of Epstein-Barr virus infection. Baillieres Best Pract Res Clin Haematol 13:199–214

    Article  PubMed  CAS  Google Scholar 

  • Pati S, Cavrois M, Guo HG, Foulke JS Jr, Kim J, Feldman RA, Reitz M (2001) Activation of NF-kappaB by the human herpesvirus 8 chemokine receptor ORF74: evidence for a paracrine model of Kaposi’s sarcoma pathogenesis. J Virol 75:8660–8673

    Article  PubMed  CAS  Google Scholar 

  • Paudel N, Sadagopan S, Balasubramanian S, Chandran B (2012) Kaposi’s Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen and Angiogenin Interact with Common Host Proteins, Including Annexin A2, Which Is Essential for Survival of Latently Infected Cells. J Virol 86:1589–1607

    Article  PubMed  CAS  Google Scholar 

  • Paulose-Murphy M, Ha NK, Xiang C, Chen Y, Gillim L, Yarchoan R, Meltzer P, Bittner M, Trent J, Zeichner S (2001) Transcription program of human herpesvirus 8 (kaposi’s sarcoma-associated herpesvirus). J Virol 75:4843–4853

    Article  PubMed  CAS  Google Scholar 

  • Pearce M, Matsumura S, Wilson AC (2005) Transcripts encoding K12, v-FLIP, v-cyclin, and the microRNA cluster of Kaposi’s sarcoma-associated herpesvirus originate from a common promoter. J Virol 79:14457–14464

    Article  PubMed  CAS  Google Scholar 

  • Petre CE, Sin SH, Dittmer DP (2007) Functional p53 signaling in Kaposi’s sarcoma-associated herpesvirus lymphomas: implications for therapy. J Virol 81:1912–1922

    Article  PubMed  CAS  Google Scholar 

  • Pfeffer S, Sewer A, Lagos-Quintana M, Sheridan R, Sander C, Grasser FA, van Dyk LF, Ho CK, Shuman S, Chien M, Russo JJ, Ju J, Randall G, Lindenbach BD, Rice CM, Simon V, Ho DD, Zavolan M, Tuschl T (2005) Identification of microRNAs of the herpesvirus family. Nat Methods 2:269–276

    Article  PubMed  CAS  Google Scholar 

  • Pfeffer S, Zavolan M, Grasser FA, Chien M, Russo JJ, Ju J, John B, Enright AJ, Marks D, Sander C, Tuschl T (2004) Identification of virus-encoded microRNAs. Science 304:734–736

    Article  PubMed  CAS  Google Scholar 

  • Philpott N, Bakken T, Pennell C, Chen L, Wu J, Cannon M (2011) The Kaposi’s sarcoma-associated herpesvirus G protein-coupled receptor contains an immunoreceptor tyrosine-based inhibitory motif that activates Shp2. J Virol 85:1140–1144

    Article  PubMed  CAS  Google Scholar 

  • Pietrek M, Brinkmann MM, Glowacka I, Enlund A, Havemeier A, Dittrich-Breiholz O, Kracht M, Lewitzky M, Saksela K, Feller SM, Schulz TF (2010) Role of the Kaposi’s sarcoma-associated herpesvirus K15 SH3 binding site in inflammatory signaling and B-cell activation. J Virol 84:8231–8240

    Article  PubMed  CAS  Google Scholar 

  • Platt G, Carbone A, Mittnacht S (2002) p16INK4a loss and sensitivity in KSHV associated primary effusion lymphoma. Oncogene 21:1823–1831

    Article  PubMed  CAS  Google Scholar 

  • Poole LJ, Zong JC, Ciufo DM, Alcendor DJ, Cannon JS, Ambinder R, Orenstein JM, Reitz MS, Hayward GS (1999) Comparison of genetic variability at multiple loci across the genomes of the major subtypes of Kaposi’s sarcoma-associated herpesvirus reveals evidence for recombination and for two distinct types of open reading frame K15 alleles at the right-hand end. J Virol 73:6646–6660

    PubMed  CAS  Google Scholar 

  • Pozharskaya VP, Weakland LL, Zimring JC, Krug LT, Unger ER, Neisch A, Joshi H, Inoue N, Offermann MK (2004) Short duration of elevated vIRF-1 expression during lytic replication of human herpesvirus 8 limits its ability to block antiviral responses induced by alpha interferon in BCBL-1 cells. J Virol 78:6621–6635

    Article  PubMed  CAS  Google Scholar 

  • Prakash O, Tang ZY, Peng X, Coleman R, Gill J, Farr G, Samaniego F (2002) Tumorigenesis and aberrant signaling in transgenic mice expressing the human herpesvirus-8 K1 gene. J Natl Cancer Inst 94:926–935

    Article  PubMed  CAS  Google Scholar 

  • Pyakurel P, Pak F, Mwakigonja AR, Kaaya E, Heiden T, Biberfeld P (2006) Lymphatic and vascular origin of Kaposi’s sarcoma spindle cells during tumor development. Int J Cancer 119:1262–1267

    Article  PubMed  CAS  Google Scholar 

  • Qin Z, Freitas E, Sullivan R, Mohan S, Bacelieri R, Branch D, Romano M, Kearney P, Oates J, Plaisance K, Renne R, Kaleeba J, Parsons C (2010) Upregulation of xCT by KSHV-encoded microRNAs facilitates KSHV dissemination and persistence in an environment of oxidative stress. PLoS Pathog 6:e1000742

    Article  PubMed  CAS  Google Scholar 

  • Radkov SA, Kellam P, Boshoff C (2000) The latent nuclear antigen of Kaposi sarcoma-associated herpesvirus targets the retinoblastoma-E2F pathway and with the oncogene Hras transforms primary rat cells. Nat Med 6:1121–1127

    Article  PubMed  CAS  Google Scholar 

  • Rivas C, Thlick AE, Parravicini C, Moore PS, Chang Y (2001) Kaposi’s sarcoma-associated herpesvirus LANA2 is a B-cell-specific latent viral protein that inhibits p53. J Virol 75:429–438

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, van Dongen S, Grocock RJ, Das PP, Miska EA, Vetrie D, Okkenhaug K, Enright AJ, Dougan G, Turner M, Bradley A (2007) Requirement of bic/microRNA-155 for normal immune function. Science 316:608–611

    Article  PubMed  CAS  Google Scholar 

  • Rosenkilde MM, Waldhoer M, Luttichau HR, Schwartz TW (2001) Virally encoded 7TM receptors. Oncogene 20:1582–1593

    Article  PubMed  CAS  Google Scholar 

  • Roth WK (1991) HIV-associated Kaposi’s sarcoma: new developments in epidemiology and molecular pathology. J Cancer Res Clin Oncol 117:186–191

    Article  PubMed  CAS  Google Scholar 

  • Russo JJ, Bohenzky RA, Chien MC, Chen J, Yan M, Maddalena D, Parry JP, Peruzzi D, Edelman IS, Chang Y, Moore PS (1996) Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc Natl Acad Sci U S A 93:14862–14867

    Article  PubMed  CAS  Google Scholar 

  • Sadagopan S, Sharma-Walia N, Veettil MV, Bottero V, Levine R, Vart RJ, Chandran B (2009) Kaposi’s sarcoma-associated herpesvirus upregulates angiogenin during infection of human dermal microvascular endothelial cells, which induces 45S rRNA synthesis, antiapoptosis, cell proliferation, migration, and angiogenesis. J Virol 83:3342–3364

    Article  PubMed  CAS  Google Scholar 

  • Sadagopan S, Valiya Veettil M, Paudel N, Bottero V, Chandran B (2011) Kaposi’s sarcoma-associated herpesvirus-induced angiogenin plays roles in latency via the phospholipase C gamma pathway: blocking angiogenin inhibits latent gene expression and induces the lytic cycle. J Virol 85:2666–2685

    Article  PubMed  CAS  Google Scholar 

  • Sadagopan S, Veettil MV, Chakraborty S, Sharma-Walia N, Paudel N, Bottero V, Chandran B (2012) Angiogenin functionally interacts with p53 and regulates p53-mediated apoptosis and cell survival. Oncogene 31:4835–4847

    Google Scholar 

  • Sadler R, Wu L, Forghani B, Renne R, Zhong W, Herndier B, Ganem D (1999) A complex translational program generates multiple novel proteins from the latently expressed kaposin (K12) locus of Kaposi’s sarcoma-associated herpesvirus. J Virol 73:5722–5730

    PubMed  CAS  Google Scholar 

  • Sakakibara S, Ueda K, Nishimura K, Do E, Ohsaki E, Okuno T, Yamanishi K (2004) Accumulation of heterochromatin components on the terminal repeat sequence of Kaposi’s sarcoma-associated herpesvirus mediated by the latency-associated nuclear antigen. J Virol 78:7299–7310

    Article  PubMed  CAS  Google Scholar 

  • Samaniego F, Pati S, Karp JE, Prakash O, Bose D (2001) Human herpesvirus 8 K1-associated nuclear factor-kappa B-dependent promoter activity: role in Kaposi’s sarcoma inflammation? J Natl Cancer Inst Monogr 28:15–23

    Google Scholar 

  • Samols MA, Hu J, Skalsky RL, Renne R (2005) Cloning and identification of a microRNA cluster within the latency-associated region of Kaposi’s sarcoma-associated herpesvirus. J Virol 79:9301–9305

    Article  PubMed  CAS  Google Scholar 

  • Samols MA, Skalsky RL, Maldonado AM, Riva A, Lopez MC, Baker HV, Renne R (2007) Identification of cellular genes targeted by KSHV-encoded microRNAs. PLoS Pathogens 3:e65

    Google Scholar 

  • Sandford G, Choi YB, Nicholas J (2009) Role of ORF74-encoded viral G protein-coupled receptor in human herpesvirus 8 lytic replication. J Virol 83:13009–13014

    Google Scholar 

  • Schmidt K, Wies E, Neipel F (2011) Kaposi’s sarcoma-associated herpesvirus viral interferon regulatory factor 3 inhibits gamma interferon and major histocompatibility complex class II expression. J Virol 85:4530–4537

    Article  PubMed  CAS  Google Scholar 

  • Schwarz DS, Hutvagner G, Du T, Xu Z, Aronin N, Zamore PD (2003) Asymmetry in the assembly of the RNAi enzyme complex. Cell 115:199–208

    Article  PubMed  CAS  Google Scholar 

  • Schwarz M, Murphy PM (2001) Kaposi’s sarcoma-associated herpesvirus G protein-coupled receptor constitutively activates NF-kappa B and induces proinflammatory cytokine and chemokine production via a C-terminal signaling determinant. J Immunol 167:505–513

    PubMed  CAS  Google Scholar 

  • Searles RP, Bergquam EP, Axthelm MK, Wong SW (1999) Sequence and genomic analysis of a Rhesus macaque rhadinovirus with similarity to Kaposi’s sarcoma-associated herpesvirus/human herpesvirus 8. J Virol 73:3040–3053

    PubMed  CAS  Google Scholar 

  • Sears R, Nuckolls F, Haura E, Taya Y, Tamai K, Nevins JR (2000) Multiple Ras-dependent phosphorylation pathways regulate Myc protein stability. Genes Dev 14:2501–2514

    Article  PubMed  CAS  Google Scholar 

  • Seo T, Lee D, Lee B, Chung JH, Choe J (2000) Viral interferon regulatory factor 1 of Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) binds to, and inhibits transactivation of, CREB-binding protein. Biochem Biophys Res Commun 270:23–27

    Article  PubMed  CAS  Google Scholar 

  • Seo T, Lee D, Shim YS, Angell JE, Chidambaram NV, Kalvakolanu DV, Choe J (2002) Viral interferon regulatory factor 1 of Kaposi’s sarcoma-associated herpesvirus interacts with a cell death regulator, GRIM19, and inhibits interferon/retinoic acid-induced cell death. J Virol 76:8797–8807

    Article  PubMed  CAS  Google Scholar 

  • Seo T, Park J, Choe J (2005) Kaposi’s sarcoma-associated herpesvirus viral IFN regulatory factor 1 inhibits transforming growth factor-beta signaling. Cancer Res 65:1738–1747

    Article  PubMed  CAS  Google Scholar 

  • Seo T, Park J, Lee D, Hwang SG, Choe J (2001) Viral interferon regulatory factor 1 of Kaposi’s sarcoma-associated herpesvirus binds to p53 and represses p53-dependent transcription and apoptosis. J Virol 75:6193–6198

    Article  PubMed  CAS  Google Scholar 

  • Shamay M, Krithivas A, Zhang J, Hayward SD (2006) Recruitment of the de novo DNA methyltransferase Dnmt3a by Kaposi’s sarcoma-associated herpesvirus LANA. Proc Natl Acad Sci U S A 103:14554–14559

    Article  PubMed  CAS  Google Scholar 

  • Sharma-Walia N, Paul AG, Bottero V, Sadagopan S, Veettil MV, Kerur N, Chandran B (2010) Kaposi’s sarcoma associated herpes virus (KSHV) induced COX-2: a key factor in latency, inflammation, angiogenesis, cell survival and invasion. PLoS Pathog 6:e1000777

    Article  PubMed  CAS  Google Scholar 

  • Sharp TV, Wang HW, Koumi A, Hollyman D, Endo Y, Ye H, Du MQ, Boshoff C (2002) K15 protein of Kaposi’s sarcoma-associated herpesvirus is latently expressed and binds to HAX-1, a protein with antiapoptotic function. J Virol 76:802–816

    Article  PubMed  CAS  Google Scholar 

  • Shepard LW, Yang M, Xie P, Browning DD, Voyno-Yasenetskaya T, Kozasa T, Ye RD (2001) Constitutive activation of NF-kappa B and secretion of interleukin-8 induced by the G protein-coupled receptor of Kaposi’s sarcoma-associated herpesvirus involve G alpha(13) and RhoA. J Biol Chem 276:45979–45987

    Article  PubMed  CAS  Google Scholar 

  • Shim WS, Ho IA, Wong PE (2007) Angiopoietin: a TIE(d) balance in tumor angiogenesis. Mol Cancer Res 5:655–665

    Article  PubMed  CAS  Google Scholar 

  • Shin YC, Joo CH, Gack MU, Lee HR, Jung JU (2008) Kaposi’s sarcoma-associated herpesvirus viral IFN regulatory factor 3 stabilizes hypoxia-inducible factor-1 alpha to induce vascular endothelial growth factor expression. Cancer Res 68:1751–1759

    Article  PubMed  CAS  Google Scholar 

  • Shin YC, Nakamura H, Liang X, Feng P, Chang H, Kowalik TF, Jung JU (2006) Inhibition of the ATM/p53 signal transduction pathway by Kaposi’s sarcoma-associated herpesvirus interferon regulatory factor 1. J Virol 80:2257–2266

    Article  PubMed  CAS  Google Scholar 

  • Skalsky RL, Samols MA, Plaisance KB, Boss IW, Riva A, Lopez MC, Baker HV, Renne R (2007) Kaposi’s sarcoma-associated herpesvirus encodes an ortholog of miR-155. J Virol 81:12836–12845

    Article  PubMed  CAS  Google Scholar 

  • Staskus KA, Zhong W, Gebhard K, Herndier B, Wang H, Renne R, Beneke J, Pudney J, Anderson DJ, Ganem D, Haase AT (1997) Kaposi’s sarcoma-associated herpesvirus gene expression in endothelial (spindle) tumor cells. J Virol 71:715–719

    PubMed  CAS  Google Scholar 

  • Stern-Ginossar N, Elefant N, Zimmermann A, Wolf DG, Saleh N, Biton M, Horwitz E, Prokocimer Z, Prichard M, Hahn G, Goldman-Wohl D, Greenfield C, Yagel S, Hengel H, Altuvia Y, Margalit H, Mandelboim O (2007) Host immune system gene targeting by a viral miRNA. Science 317:376–381

    Article  PubMed  CAS  Google Scholar 

  • Stern-Ginossar N, Gur C, Biton M, Horwitz E, Elboim M, Stanietsky N, Mandelboim M, Mandelboim O (2008) Human microRNAs regulate stress-induced immune responses mediated by the receptor NKG2D. Nat Immunol 9:1065–1073

    Article  PubMed  CAS  Google Scholar 

  • 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 (2000) KSHV-encoded CC chemokine vMIP-III is a CCR4 agonist, stimulates angiogenesis, and selectively chemoattracts TH2 cells. Blood 95:1151–1157

    PubMed  CAS  Google Scholar 

  • Sturzl M, Blasig C, Schreier A, Neipel F, Hohenadl C, Cornali E, Ascherl G, Esser S, Brockmeyer NH, Ekman M, Kaaya EE, Tschachler E, Biberfeld P (1997) Expression of HHV-8 latency-associated T0.7 RNA in spindle cells and endothelial cells of AIDS-associated, classical and African Kaposi’s sarcoma. Int J Cancer 72:68–71

    Article  PubMed  CAS  Google Scholar 

  • Suffert G, Malterer G, Hausser J, Viiliainen J, Fender A, Contrant M, Ivacevic T, Benes V, Gros F, Voinnet O, Zavolan M, Ojala PM, Haas JG, Pfeffer S (2011) Kaposi’s sarcoma herpesvirus microRNAs target caspase 3 and regulate apoptosis. PLoS Pathog 7:e1002405

    Article  PubMed  CAS  Google Scholar 

  • Sun Q, Matta H, Lu G, Chaudhary PM (2006) Induction of IL-8 expression by human herpesvirus 8 encoded vFLIP K13 via NF-kappaB activation. Oncogene 25:2717–2726

    Article  PubMed  CAS  Google Scholar 

  • Sun R, Lin SF, Staskus K, Gradoville L, Grogan E, Haase A, Miller G (1999) Kinetics of Kaposi’s sarcoma-associated herpesvirus gene expression. J Virol 73:2232–2242

    PubMed  CAS  Google Scholar 

  • Thomas M, Augustin HG (2009) The role of the Angiopoietins in vascular morphogenesis. Angiogenesis 12:125–137

    Article  PubMed  CAS  Google Scholar 

  • Thome M, Schneider P, Hofmann K, Fickenscher H, Meinl E, Neipel F, Mattmann C, Burns K, Bodmer JL, Schroter M, Scaffidi C, Krammer PH, Peter ME, Tschopp J (1997) Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature 386:517–521

    Article  PubMed  CAS  Google Scholar 

  • Tomkowicz B, Singh SP, Cartas M, Srinivasan A (2002) Human herpesvirus-8 encoded Kaposin: subcellular localization using immunofluorescence and biochemical approaches. DNA Cell Biol 21:151–162

    Article  PubMed  CAS  Google Scholar 

  • Tomkowicz B, Singh SP, Lai D, Singh A, Mahalingham S, Joseph J, Srivastava S, Srinivasan A (2005) Mutational analysis reveals an essential role for the LXXLL motif in the transformation function of the human herpesvirus-8 oncoprotein, kaposin. DNA Cell Biol 24:10–20

    Article  PubMed  CAS  Google Scholar 

  • Tomlinson CC, Damania B (2004) The K1 protein of Kaposi’s sarcoma-associated herpesvirus activates the Akt signaling pathway. J Virol 78:1918–1927

    Article  PubMed  CAS  Google Scholar 

  • Tsai YH, Wu MF, Wu YH, Chang SJ, Lin SF, Sharp TV, Wang HW (2009) The M type K15 protein of Kaposi’s sarcoma-associated herpesvirus regulates microRNA expression via its SH2-binding motif to induce cell migration and invasion. J Virol 83:622–632

    Article  PubMed  CAS  Google Scholar 

  • Umbach JL, Cullen BR (2010) In-depth analysis of Kaposi’s sarcoma-associated herpesvirus microRNA expression provides insights into the mammalian microRNA-processing machinery. J Virol 84:695–703

    Article  PubMed  CAS  Google Scholar 

  • Verma SC, Lan K, Robertson E (2007) Structure and function of latency-associated nuclear antigen. Curr Top Microbiol Immunol 312:101–136

    Article  PubMed  CAS  Google Scholar 

  • Verschuren EW, Jones N, Evan GI (2004) The cell cycle and how it is steered by Kaposi’s sarcoma-associated herpesvirus cyclin. J Gen Virol 85:1347–1361

    Article  PubMed  CAS  Google Scholar 

  • Verzijl D, Fitzsimons CP, Van Dijk M, Stewart JP, Timmerman H, Smit MJ, Leurs R (2004) Differential activation of murine herpesvirus 68- and Kaposi’s sarcoma-associated herpesvirus-encoded ORF74 G protein-coupled receptors by human and murine chemokines. J Virol 78:3343–3351

    Article  PubMed  CAS  Google Scholar 

  • Wang HW, Sharp TV, Koumi A, Koentges G, Boshoff C (2002) Characterization of an anti-apoptotic glycoprotein encoded by Kaposi’s sarcoma-associated herpesvirus which resembles a spliced variant of human survivin. EMBO J 21:2602–2615

    Article  PubMed  CAS  Google Scholar 

  • Wang HW, Trotter MW, Lagos D, Bourboulia D, Henderson S, Makinen T, Elliman S, Flanagan AM, Alitalo K, Boshoff C (2004) Kaposi sarcoma herpesvirus-induced cellular reprogramming contributes to the lymphatic endothelial gene expression in Kaposi sarcoma. Nat Genet 36:687–693

    Article  PubMed  CAS  Google Scholar 

  • Wang L, Dittmer DP, Tomlinson CC, Fakhari FD, Damania B (2006) Immortalization of primary endothelial cells by the K1 protein of Kaposi’s sarcoma-associated herpesvirus. Cancer Res 66:3658–3666

    Article  PubMed  CAS  Google Scholar 

  • Weber KS, Grone HJ, Rocken M, Klier C, Gu S, Wank R, Proudfoot AE, Nelson PJ, Weber C (2001) Selective recruitment of Th2-type cells and evasion from a cytotoxic immune response mediated by viral macrophage inhibitory protein-II. Eur J Immunol 31:2458–2466

    Article  PubMed  CAS  Google Scholar 

  • Whitby D, Marshall VA, Bagni RK, Wang CD, Gamache CJ, Guzman JR, Kron M, Ebbesen P, Biggar RJ (2004) Genotypic characterization of Kaposi’s sarcoma-associated herpesvirus in asymptomatic infected subjects from isolated populations. J Gen Virol 85:155–163

    Article  PubMed  CAS  Google Scholar 

  • Wies E, Hahn AS, Schmidt K, Viebahn C, Rohland N, Lux A, Schellhorn T, Holzer A, Jung JU, Neipel F (2009) The Kaposi’s Sarcoma-associated Herpesvirus-encoded vIRF-3 Inhibits Cellular IRF-5. J Biol Chem 284:8525–8538

    Article  PubMed  CAS  Google Scholar 

  • Wies E, Mori Y, Hahn A, Kremmer E, Sturzl M, Fleckenstein B, Neipel F (2008) The viral interferon-regulatory factor-3 is required for the survival of KSHV-infected primary effusion lymphoma cells. Blood 111:320–327

    Article  PubMed  CAS  Google Scholar 

  • Willis SN, Adams JM (2005) Life in the balance: how BH3-only proteins induce apoptosis. Curr Opin Cell Biol 17:617–625

    Article  PubMed  CAS  Google Scholar 

  • Wong EL, Damania B (2006) Transcriptional regulation of the Kaposi’s sarcoma-associated herpesvirus K15 gene. J Virol 80:1385–1392

    Article  PubMed  CAS  Google Scholar 

  • Wu AL, Wang J, Zheleznyak A, Brown EJ (1999) Ubiquitin-related proteins regulate interaction of vimentin intermediate filaments with the plasma membrane. Mol Cell 4:619–625

    Article  PubMed  CAS  Google Scholar 

  • Yang TY, Chen SC, Leach MW, Manfra D, Homey B, Wiekowski M, Sullivan L, Jenh CH, Narula SK, Chensue SW, Lira SA (2000) Transgenic expression of the chemokine receptor encoded by human herpesvirus 8 induces an angioproliferative disease resembling Kaposi’s sarcoma. J Exp Med 191:445–454

    Article  PubMed  CAS  Google Scholar 

  • Yoo J, Kang J, Lee HN, Aguilar B, Kafka D, Lee S, Choi I, Lee J, Ramu S, Haas J, Koh CJ, Hong YK (2010) Kaposin-B enhances the PROX1 mRNA stability during lymphatic reprogramming of vascular endothelial cells by Kaposi’s sarcoma herpes virus. PLoS Pathog 6:e1001046

    Article  PubMed  CAS  Google Scholar 

  • Yoshizaki K, Matsuda T, Nishimoto N, Kuritani T, Taeho L, Aozasa K, Nakahata T, Kawai H, Tagoh H, Komori T et al (1989) Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman’s disease. Blood 74:1360–1367

    PubMed  CAS  Google Scholar 

  • Young LS, Murray PG (2003) Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene 22:5108–5121

    Article  PubMed  CAS  Google Scholar 

  • Zeng Y, Yi R, Cullen BR (2003) MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci U S A 100:9779–9784

    Article  PubMed  CAS  Google Scholar 

  • Zhang YJ, Bonaparte RS, Patel D, Stein DA, Iversen PL (2008) Blockade of viral interleukin-6 expression of Kaposi’s sarcoma-associated herpesvirus. Mol Cancer Ther 7:712–720

    Article  PubMed  CAS  Google Scholar 

  • Zhao J, Punj V, Matta H, Mazzacurati L, Schamus S, Yang Y, Yang T, Hong Y, Chaudhary PM (2007) K13 blocks KSHV lytic replication and deregulates vIL6 and hIL6 expression: a model of lytic replication induced clonal selection in viral oncogenesis. PLoS One 2:e1067

    Article  PubMed  CAS  Google Scholar 

  • Zhong W, Wang H, Herndier B, Ganem D (1996) Restricted expression of Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genes in Kaposi sarcoma. Proc Natl Acad Sci U S A 93:6641–6646

    Article  PubMed  CAS  Google Scholar 

  • Ziech D, Franco R, Pappa A, Malamou-Mitsi V, Georgakila S, Georgakilas AG, Panayiotidis MI (2010) The role of epigenetics in environmental and occupational carcinogenesis. Chem Biol Interact 188:340–349

    Article  PubMed  CAS  Google Scholar 

  • Ziegelbauer JM, Sullivan CS, Ganem D (2009) Tandem array-based expression screens identify host mRNA targets of virus-encoded microRNAs. Nat Genet 41:130–134

    Article  PubMed  CAS  Google Scholar 

  • Zimring JC, Goodbourn S, Offermann MK (1998) Human herpesvirus 8 encodes an interferon regulatory factor (IRF) homolog that represses IRF-1-mediated transcription. J Virol 72:701–707

    PubMed  CAS  Google Scholar 

  • Zong JC, Ciufo DM, Alcendor DJ, Wan X, Nicholas J, Browning PJ, Rady PL, Tyring SK, Orenstein JM, Rabkin CS, Su IJ, Powell KF, Croxson M, Foreman KE, Nickoloff BJ, Alkan S, Hayward GS (1999) High-level variability in the ORF-K1 membrane protein gene at the left end of the Kaposi’s sarcoma-associated herpesvirus genome defines four major virus subtypes and multiple variants or clades in different human populations. J Virol 73:4156–4170

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Baltimore, MD, 21287, USA

    Emily Cousins & John Nicholas

Authors
  1. Emily Cousins
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John Nicholas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John Nicholas .

Editor information

Editors and Affiliations

  1. Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan

    Mei Hwei Chang

  2. Molecular Virology Section, Lab. of Mole, National Institute of Allergy and Infect, Bethesda, Maryland, USA

    Kuan-Teh Jeang

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Cousins, E., Nicholas, J. (2014). Molecular Biology of Human Herpesvirus 8: Novel Functions and Virus–Host Interactions Implicated in Viral Pathogenesis and Replication. In: Chang, M., Jeang, KT. (eds) Viruses and Human Cancer. Recent Results in Cancer Research, vol 193. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38965-8_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-38965-8_13

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-38964-1

  • Online ISBN: 978-3-642-38965-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation