Abstract
Signal transduction pathways play a key role in the regulation of cell growth, cell differentiation, cell survival, apoptosis, and immune responses. Bacterial and viral pathogens utilize the cell signal pathways by encoding their own proteins or noncoding RNAs to serve their survival and replication in infected cells. Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is classified as a rhadinovirus in the γ-herpesvirus subfamily and was the eighth human herpesvirus to be discovered from Kaposi’s sarcoma specimens. KSHV is closely associated with an endothelial cell malignancy, Kaposi’s sarcoma, and B-cell malignancies, primary effusion lymphoma, and multicentric Castleman’s disease. Recent studies have revealed that KSHV manipulates the cellular signaling pathways to achieve persistent infection, viral replication, cell proliferation, anti-apoptosis, and evasion of immune surveillance in infected cells. This chapter summarizes recent developments in our understanding of the molecular mechanisms used by KSHV to interact with the cell signaling machinery.
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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(23):12139–12151. https://doi.org/10.1128/jvi.00884-10
Adams JM, Cory S (1998) The Bcl-2 protein family: arbiters of cell survival. Sci ( NY) 281(5381):1322–1326
Akula SM, Ford PW, Whitman AG, Hamden KE, Shelton JG, McCubrey JA (2004) Raf promotes human herpesvirus-8 (HHV-8/KSHV) infection. Oncogene 23(30):5227–5241. https://doi.org/10.1038/sj.onc.1207643
Akula SM, Pramod NP, Wang FZ, Chandran B (2001a) Human herpesvirus 8 envelope-associated glycoprotein B interacts with heparan sulfate-like moieties. Virology 284(2):235–249. https://doi.org/10.1006/viro.2001.0921
Akula SM, Pramod NP, Wang FZ, Chandran B (2002) Integrin alpha3beta1 (CD 49c/29) is a cellular receptor for Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8) entry into the target cells. Cell 108(3):407–419
Akula SM, Wang FZ, Vieira J, Chandran B (2001b) Human herpesvirus 8 interaction with target cells involves heparan sulfate. Virology 282(2):245–255. https://doi.org/10.1006/viro.2000.0851
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(35):23272–23285. https://doi.org/10.1074/jbc.M109.033290
Arias C, Weisburd B, Stern-Ginossar N, Mercier A, Madrid AS, Bellare P, Holdorf M, Weissman JS, Ganem D (2014) KSHV 2.0: a comprehensive annotation of the Kaposi’s sarcoma-associated herpesvirus genome using next-generation sequencing reveals novel genomic and functional features. PLoS Pathog 10(1):e1003847. https://doi.org/10.1371/journal.ppat.1003847
Arvanitakis L, Geras-Raaka E, Varma A, Gershengorn MC, Cesarman E (1997) Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation. Nature 385(6614):347–350. https://doi.org/10.1038/385347a0
Bai Z, Huang Y, Li W, Zhu Y, Jung JU, Lu C, Gao SJ (2014) Genomewide mapping and screening of Kaposi’s sarcoma-associated herpesvirus (KSHV) 3′ untranslated regions identify bicistronic and polycistronic viral transcripts as frequent targets of KSHV microRNAs. J Virol 88(1):377–392. https://doi.org/10.1128/jvi.02689-13
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(6662):86–89. https://doi.org/10.1038/34193
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. Sci (NY) 311(5762):856–861. https://doi.org/10.1126/science.1120541
Baresova P, Musilova J, Pitha PM, Lubyova B (2014) p53 tumor suppressor protein stability and transcriptional activity are targeted by Kaposi’s sarcoma-associated herpesvirus-encoded viral interferon regulatory factor 3. Mol Cell Biol 34(3):386–399. https://doi.org/10.1128/MCB.01011-13
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297. https://doi.org/10.1016/S0092-8674(04)00045-5
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(6):570–575. https://doi.org/10.1016/j.chom.2009.11.008
Bhatt AP, Damania B (2012) AKTivation of PI3K/AKT/mTOR signaling pathway by KSHV. Front Immunol 3:401. https://doi.org/10.3389/fimmu.2012.00401
Borah S, Darricarrere N, Darnell A, Myoung J, Steitz JA (2011) A viral nuclear noncoding RNA binds re-localized poly(A) binding protein and is required for late KSHV gene expression. PLoS Pathog 7(10):e1002300. https://doi.org/10.1371/journal.ppat.1002300
Bottero V, Kerur N, Sadagopan S, Patel K, Sharma-Walia N, Chandran B (2011) Phosphorylation and polyubiquitination of transforming growth factor beta-activated kinase 1 are necessary for activation of NF-kappaB by the Kaposi’s sarcoma-associated herpesvirus G protein-coupled receptor. J Virol 85(5):1980–1993. https://doi.org/10.1128/jvi.01911-10
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(17):9346–9358
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(1):42–58. https://doi.org/10.1128/jvi.00648-06
Brinkmann MM, Schulz TF (2006) Regulation of intracellular signalling by the terminal membrane proteins of members of the Gammaherpesvirinae. J Gen Virol 87(Pt 5):1047–1074. https://doi.org/10.1099/vir.0.81598-0
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(34):4979–4986. https://doi.org/10.1038/sj.onc.1210299
Burysek L, Yeow WS, Lubyova B, Kellum M, Schafer SL, Huang YQ, Pitha PM (1999) 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(9):7334–7342
Buryýšek L, Pitha PM (2001) Latently expressed human herpesvirus 8-encoded interferon regulatory factor 2 inhibits double-stranded RNA-activated protein kinase. J Virol 75(5):2345–2352. https://doi.org/10.1128/JVI.75.5.2345-2352.2001
Cai Q-L, Knight JS, Verma SC, Zald P, Robertson ES (2006) EC(5)S ubiquitin complex Is recruited by KSHV latent antigen LANA for degradation of the VHL and p53 tumor suppressors. PLoS Pathog 2(10):e116. https://doi.org/10.1371/journal.ppat.0020116
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 USA 102(15):5570–5575. https://doi.org/10.1073/pnas.0408192102
Campbell M, Kim KY, Chang PC, Huerta S, Shevchenko B, Wang DH, Izumiya C, Kung HJ, Izumiya Y (2014a) A lytic viral long noncoding RNA modulates the function of a latent protein. J Virol 88(3):1843–1848. https://doi.org/10.1128/jvi.03251-13
Campbell M, Kung HJ, Izumiya Y (2014b) Long non-coding RNA and epigenetic gene regulation of KSHV. Viruses 6(11):4165–4177. https://doi.org/10.3390/v6114165
Cannon JS, Nicholas J, Orenstein JM, Mann RB, Murray PG, Browning PJ, DiGiuseppe JA, Cesarman E, Hayward GS, Ambinder RF (1999) Heterogeneity of viral IL-6 expression in HHV-8-associated diseases. J Infect Dis 180(3):824–828. https://doi.org/10.1086/314956
Cannon ML, Cesarman E (2004) The KSHV G protein-coupled receptor signals via multiple pathways to induce transcription factor activation in primary effusion lymphoma cells. Oncogene 23(2):514–523. https://doi.org/10.1038/sj.onc.1207021
Carroll PA, Brazeau E, Lagunoff M (2004) Kaposi’s sarcoma-associated herpesvirus infection of blood endothelial cells induces lymphatic differentiation. Virology 328(1):7–18. https://doi.org/10.1016/j.virol.2004.07.008
Cesarman E, Nador RG, Bai F, Bohenzky RA, Russo JJ, Moore PS, Chang Y, Knowles DM (1996) Kaposi’s sarcoma-associated herpesvirus contains G protein-coupled receptor and cyclin D homologs which are expressed in Kaposi’s sarcoma and malignant lymphoma. J Virol 70(11):8218–8223
Chandriani S, Xu Y, Ganem D (2010) The lytic transcriptome of Kaposi’s sarcoma-associated herpesvirus reveals extensive transcription of noncoding regions, including regions antisense to important genes. J Virol 84(16):7934–7942. https://doi.org/10.1128/JVI.00645-10
Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS (1994) Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science (New York, NY) 266(5192):1865–1869
Chang Y, Moore PS, Talbot SJ, Boshoff CH, Zarkowska T, Godden K, Paterson H, Weiss RA, Mittnacht S (1996) Cyclin encoded by KS herpesvirus. Nature 382(6590):410. https://doi.org/10.1038/382410a0
Chau BN, Cheng EH, Kerr DA, Hardwick JM (2000) Aven, a novel inhibitor of caspase activation, binds Bcl-xL and Apaf-1. Mol Cell 6(1):31–40
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(42):5738–5746. https://doi.org/10.1038/sj.onc.1202976
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(19):9811–9821. https://doi.org/10.1128/JVI.00872-06
Chen J, Jiang L, Lan K, Chen X (2015) Celecoxib inhibits the lytic activation of Kaposi’s sarcoma-associated herpesvirus through down-regulation of RTA expression by inhibiting the activation of p38 MAPK. Viruses 7(5):2268–2287. https://doi.org/10.3390/v7052268
Cheng EH, Nicholas J, Bellows DS, Hayward GS, Guo HG, Reitz MS, Hardwick JM (1997) A Bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with Bax or Bak. Proc Natl Acad Sci U S A 94(2):690–694
Choi J, Means RE, Damania B, Jung JU (2001) Molecular piracy of Kaposi’s sarcoma associated herpesvirus. Cytokine Growth Factor Rev 12(2-3):245–257
Choi YB, Nicholas J (2010) Bim nuclear translocation and inactivation by viral interferon regulatory factor. PLoS Pathog 6(8):e1001031. https://doi.org/10.1371/journal.ppat.1001031
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. https://doi.org/10.1371/journal.ppat.1002748
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(36):12885–12890. https://doi.org/10.1073/pnas.0408577102
Cohen A, Brodie C, Sarid R (2006) An essential role of ERK signalling in TPA-induced reactivation of Kaposi’s sarcoma-associated herpesvirus. The Journal of general virology 87(Pt 4):795–802. https://doi.org/10.1099/vir.0.81619-0
Conrad NK (2016) New insights into the expression and functions of the Kaposi’s sarcoma-associated herpesvirus long noncoding PAN RNA. Virus Res 212:53–63. https://doi.org/10.1016/j.virusres.2015.06.012
Corcoran JA, Johnston BP, McCormick C (2015) Viral activation of MK2-hsp27-p115RhoGEF-RhoA signaling axis causes cytoskeletal rearrangements, p-body disruption and ARE-mRNA stabilization. PLoS Pathog 11(1):e1004597. https://doi.org/10.1371/journal.ppat.1004597
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(36):33805–33811. https://doi.org/10.1074/jbc.M104631200
Damania B, Cesarman E (2013) Kaposi’s sarcoma–associated herpesvirus. In: Knipe DM, Howley PM (eds) Fields virology, vol 2, 6th edn. Lippincott Williams & Wilkins, Philadelphia, pp 2080–2128
Danial NN, Korsmeyer SJ (2004) Cell death: critical control points. Cell 116(2):205–219
Deng H, Liang Y, Sun R (2007) Regulation of KSHV lytic gene expression. Curr Top Microbiol Immunol 312:157–183
Dhillon AS, Hagan S, Rath O, Kolch W (2007) MAP kinase signalling pathways in cancer. Oncogene 26(22):3279–3290. https://doi.org/10.1038/sj.onc.1210421
Dittmer D, Lagunoff M, Renne R, Staskus K, Haase A, Ganem D (1998) A cluster of latently expressed genes in Kaposi’s sarcoma-associated herpesvirus. J Virol 72(10):8309–8315
Ellis M, Chew YP, Fallis L, Freddersdorf S, Boshoff C, Weiss RA, Lu X, Mittnacht S (1999) Degradation of p27(Kip) cdk inhibitor triggered by Kaposi’s sarcoma virus cyclin-cdk6 complex. EMBO J 18(3):644–653. https://doi.org/10.1093/emboj/18.3.644
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. The Journal of general virology 84(Pt 6):1463–1470. https://doi.org/10.1099/vir.0.19014-0
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(22):11491–11504
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(9):3938–3948
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(Pt 18):3721–3728. https://doi.org/10.1242/jcs.00691
Ford PW, Bryan BA, Dyson OF, Weidner DA, Chintalgattu V, Akula SM (2006) Raf/MEK/ERK signalling triggers reactivation of Kaposi’s sarcoma-associated herpesvirus latency. J Gen Virol 87(Pt 5):1139–1144. https://doi.org/10.1099/vir.0.81628-0
Friborg J Jr, Kong W, Hottiger MO, Nabel GJ (1999) p53 inhibition by the LANA protein of KSHV protects against cell death. Nature 402(6764):889–894. https://doi.org/10.1038/47266
Fu B, Kuang E, Li W, Avey D, Li X, Turpin Z, Valdes A, Brulois K, Myoung J, Zhu F (2015) Activation of p90 ribosomal S6 kinases by ORF45 of Kaposi’s sarcoma-associated herpesvirus is critical for optimal production of infectious viruses. J Virol 89(1):195–207. https://doi.org/10.1128/jvi.01937-14
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(14):8019–8030
Fujimuro M, Liu J, Zhu J, Yokosawa H, Hayward SD (2005) Regulation of the interaction between glycogen synthase kinase 3 and the Kaposi’s sarcoma-associated herpesvirus latency-associated nuclear antigen. J Virol 79(16):10429–10441. https://doi.org/10.1128/jvi.79.16.10429-10441.2005
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(3):300–306. https://doi.org/10.1038/nm829
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(6):3092–3097. https://doi.org/10.1128/jvi.80.6.3092-3097.2006
Gallaher AM, Das S, Xiao Z, Andresson T, Kieffer-Kwon P, Happel C, Ziegelbauer J (2013) Proteomic screening of human targets of viral microRNAs reveals functions associated with immune evasion and angiogenesis. PLoS Pathog 9(9):e1003584. https://doi.org/10.1371/journal.ppat.1003584
Gao SJ, Boshoff C, Jayachandra S, Weiss RA, Chang Y, Moore PS (1997) KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway. Oncogene 15(16):1979–1985. https://doi.org/10.1038/sj.onc.1201571
Godden-Kent D, Talbot SJ, Boshoff C, Chang Y, Moore P, Weiss RA, Mittnacht S (1997) The cyclin encoded by Kaposi’s sarcoma-associated herpesvirus stimulates cdk6 to phosphorylate the retinoblastoma protein and histone H1. J Virol 71(6):4193–4198
Gottwein E, Cullen BR (2010) A human herpesvirus microRNA inhibits p21 expression and attenuates p21-mediated cell cycle arrest. J Virol 84(10):5229–5237. https://doi.org/10.1128/jvi.00202-10
Gottwein E, Mukherjee N, Sachse C, Frenzel C, Majoros WH, Chi J-TA, Braich R, Manoharan M, Soutschek J, Ohler U, Cullen BR (2007) A viral microRNA functions as an ortholog of cellular miR-155. Nature 450(7172):1096–1099. https://doi.org/10.1038/nature05992
Grundhoff A, Ganem D (2003) The latency-associated nuclear antigen of Kaposi’s sarcoma-associated herpesvirus permits replication of terminal repeat-containing plasmids. J Virol 77(4):2779–2783
Guasparri I, Keller SA, Cesarman E (2004) KSHV vFLIP is essential for the survival of infected lymphoma cells. J Exp Med 199(7):993–1003. https://doi.org/10.1084/jem.20031467
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(1):114–119. https://doi.org/10.1038/sj.embor.7400580
Haecker I, Gay LA, Yang Y, Hu J, Morse AM, McIntyre LM, Renne R (2012) Ago HITS-CLIP expands understanding of Kaposi’s sarcoma-associated herpesvirus miRNA function in primary effusion lymphomas. PLoS Pathog 8(8):e1002884. https://doi.org/10.1371/journal.ppat.1002884
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(2):195–205. https://doi.org/10.1101/gad.553410
Havemeier A, Gramolelli S, Pietrek M, Jochmann R, Sturzl M, Schulz TF (2014) 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. J Virol 88(22):13161–13172. https://doi.org/10.1128/jvi.01766-14
Hayward SD, Liu J, Fujimuro M (2006) Notch and Wnt signaling: mimicry and manipulation by gamma herpesviruses. Sci STKE Signal Transduction Knowl Environ 2006(335):re4. https://doi.org/10.1126/stke.3352006re4
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(23):12255–12264. https://doi.org/10.1128/jvi.01484-10
Hengartner MO (2000) The biochemistry of apoptosis. Nature 407(6805):770–776. https://doi.org/10.1038/35037710
Hiscott J, Nguyen TL, Arguello M, Nakhaei P, Paz S (2006) Manipulation of the nuclear factor-kappaB pathway and the innate immune response by viruses. Oncogene 25(51):6844–6867. https://doi.org/10.1038/sj.onc.1209941
Hong YK, Foreman K, Shin JW, Hirakawa S, Curry CL, Sage DR, Libermann T, Dezube BJ, Fingeroth JD, Detmar M (2004) Lymphatic reprogramming of blood vascular endothelium by Kaposi sarcoma-associated herpesvirus. Nat Genet 36(7):683–685. https://doi.org/10.1038/ng1383
Hu H, Dong J, Liang D, Gao Z, Bai L, Sun R, Hu H, Zhang H, Dong Y, Lan K (2015) Genome-wide mapping of the binding sites and structural analysis of Kaposi’s sarcoma-associated herpesvirus viral interferon regulatory factor 2 reveal that it is a DNA-binding transcription factor. J Virol 90(3):1158–1168. https://doi.org/10.1128/jvi.01392-15
Hu J, Garber AC, Renne R (2002) The latency-associated nuclear antigen of Kaposi’s sarcoma-associated herpesvirus supports latent DNA replication in dividing cells. J Virol 76(22):11677–11687
Huang Q, Petros AM, Virgin HW, Fesik SW, Olejniczak ET (2002) Solution structure of a Bcl-2 homolog from Kaposi sarcoma virus. Proc Natl Acad Sci USA 99(6):3428–3433. https://doi.org/10.1073/pnas.062525799
Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer JL, Schroter M, Burns K, Mattmann C, Rimoldi D, French LE, Tschopp J (1997) Inhibition of death receptor signals by cellular FLIP. Nature 388(6638):190–195. https://doi.org/10.1038/40657
Izumiya Y, Izumiya C, Hsia D, Ellison TJ, Luciw PA, Kung HJ (2009) NF-kappaB serves as a cellular sensor of Kaposi’s sarcoma-associated herpesvirus latency and negatively regulates K-Rta by antagonizing the RBP-Jkappa coactivator. J Virol 83(9):4435–4446. https://doi.org/10.1128/jvi.01999-08
Jacobs SR, Damania B (2011) The viral interferon regulatory factors of KSHV: immunosuppressors or oncogenes? Front Immunol 2:19. https://doi.org/10.3389/fimmu.2011.00019
Jarviluoma A, Koopal S, Rasanen S, Makela TP, Ojala PM (2004) KSHV viral cyclin binds to p27KIP1 in primary effusion lymphomas. Blood 104(10):3349–3354. https://doi.org/10.1182/blood-2004-05-1798
Jham BC, Ma T, Hu J, Chaisuparat R, Friedman ER, Pandolfi PP, Schneider A, Sodhi A, Montaner S (2011) Amplification of the angiogenic signal through the activation of the TSC/mTOR/HIF axis by the KSHV vGPCR in Kaposi’s sarcoma. PLoS One 6(4):e19103. https://doi.org/10.1371/journal.pone.0019103
Jin Y, He Z, Liang D, Zhang Q, Zhang H, Deng Q, Robertson ES, Lan K (2012) Carboxyl-terminal amino acids 1052 to 1082 of the latency-associated nuclear antigen (LANA) interact with RBP-Jkappa and are responsible for LANA-mediated RTA repression. J Virol 86(9):4956–4969. https://doi.org/10.1128/jvi.06788-11
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(15):8282–8292. https://doi.org/10.1128/jvi.00235-07
Keller SA, Schattner EJ, Cesarman E (2000) Inhibition of NF-kappaB induces apoptosis of KSHV-infected primary effusion lymphoma cells. Blood 96(7):2537–2542
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(4):833–843
Konrad A, Wies E, Thurau M, Marquardt G, Naschberger E, Hentschel S, Jochmann R, Schulz TF, Erfle H, Brors B, Lausen B, Neipel F, Sturzl M (2009) A systems biology approach to identify the combination effects of human herpesvirus 8 genes on NF-kappaB activation. J Virol 83(6):2563–2574. https://doi.org/10.1128/jvi.01512-08
Krieg A, Mahotka C, Krieg T, Grabsch H, Müller W, Takeno S, Suschek CV, Heydthausen M, Gabbert HE, Gerharz CD (2002) Expression of different survivin variants in gastric carcinomas: first clues to a role of survivin-2B in tumour progression. Br J Cancer 86(5):737–743. https://doi.org/10.1038/sj.bjc.6600153
Krueger A, Baumann S, Krammer PH, Kirchhoff S (2001) FLICE-inhibitory proteins: regulators of death receptor-mediated apoptosis. Mol Cell Biol 21(24):8247–8254. https://doi.org/10.1128/mcb.21.24.8247-8254.2001
Kuang E, Tang Q, Maul GG, Zhu F (2008) Activation of p90 ribosomal S6 kinase by ORF45 of Kaposi’s sarcoma-associated herpesvirus and its role in viral lytic replication. J Virol 82(4):1838–1850. https://doi.org/10.1128/JVI.02119-07
Kuang E, Wu F, Zhu F (2009) Mechanism of sustained activation of ribosomal S6 kinase (RSK) and ERK by kaposi sarcoma-associated herpesvirus ORF45: multiprotein complexes retain active phosphorylated ERK AND RSK and protect them from dephosphorylation. J Biol Chem 284(20):13958–13968. https://doi.org/10.1074/jbc.M900025200
Lagunoff M, Ganem D (1997) The structure and coding organization of the genomic termini of Kaposi’s sarcoma-associated herpesvirus. Virology 236(1):147–154
Laman H, Coverley D, Krude T, Laskey R, Jones N (2001) Viral cyclin-cyclin-dependent kinase 6 complexes initiate nuclear DNA replication. Mol Cell Biol 21(2):624–635. https://doi.org/10.1128/mcb.21.2.624-635.2001
Lan K, Kuppers DA, Verma SC, Robertson ES (2004) Kaposi’s sarcoma-associated herpesvirus-encoded latency-associated nuclear antigen inhibits lytic replication by targeting Rta: a potential mechanism for virus-mediated control of latency. J Virol 78(12):6585–6594. https://doi.org/10.1128/jvi.78.12.6585-6594.2004
Lan K, Verma SC, Murakami M, Bajaj B, Kaul R, Robertson ES (2007) Kaposi’s sarcoma herpesvirus-encoded latency-associated nuclear antigen stabilizes intracellular activated Notch by targeting the Sel10 protein. Proc Natl Acad Sci U S A 104(41):16287–16292. https://doi.org/10.1073/pnas.0703508104
Lavrik IN, Golks A, Krammer PH (2005) Caspases: pharmacological manipulation of cell death. J Clin Investig 115(10):2665–2672. https://doi.org/10.1172/JCI26252
Lee H, Guo J, Li M, Choi J-K, 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(9):5219–5228
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(4):435–440
Lee H-R, Choi W-C, Lee S, Hwang J, Hwang E, Guchhait K, Haas J, Toth Z, Jeon YH, Oh T-K, Kim MH, Jung JU (2011) Bilateral inhibition of HAUSP deubiquitinase by a viral interferon regulatory factor protein. Nat Struct Mol Biol 18(12):1336–1344. https://doi.org/10.1038/nsmb.2142
Lee HR, Doganay S, Chung B, Toth Z, Brulois K, Lee S, Kanketayeva Z, Feng P, Ha T, Jung JU (2014) Kaposi’s sarcoma-associated herpesvirus viral interferon regulatory factor 4 (vIRF4) targets expression of cellular IRF4 and the Myc gene to facilitate lytic replication. J Virol 88(4):2183–2194. https://doi.org/10.1128/jvi.02106-13
Lee HR, Mitra J, Lee S, Gao SJ, Oh TK, Kim MH, Ha T, Jung JU (2015) Kaposi’s sarcoma-associated herpesvirus viral interferon regulatory factor 4 (vIRF4) perturbs the G1-S cell cycle progression via deregulation of the cyclin D1 Gene. J Virol 90(2):1139–1143. https://doi.org/10.1128/jvi.01897-15
Lee HR, Toth Z, Shin YC, Lee JS, Chang H, Gu W, Oh TK, Kim MH, Jung JU (2009) Kaposi’s sarcoma-associated herpesvirus viral interferon regulatory factor 4 targets MDM2 to deregulate the p53 tumor suppressor pathway. J Virol 83(13):6739–6747. https://doi.org/10.1128/jvi.02353-08
Lefort S, Soucy-Faulkner A, Grandvaux N, Flamand L (2007) Binding of Kaposi’s sarcoma-associated herpesvirus K-bZIP to interferon-responsive factor 3 elements modulates antiviral gene expression. J Virol 81(20):10950–10960. https://doi.org/10.1128/jvi.00183-07
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(2):193–199. https://doi.org/10.1038/ncb2019
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(21):8254–8263
Li Q, Means R, Lang S, Jung JU (2007) Downregulation of gamma interferon receptor 1 by Kaposi’s sarcomaassociated herpesvirus K3 and K5. J Virol 81(5):2117–2127. https://doi.org/10.1128/jvi.01961-06
Liang Y, Ganem D (2003) Lytic but not latent infection by Kaposi’s sarcoma-associated herpesvirus requires host CSL protein, the mediator of Notch signaling. Proc Natl Acad Sci U S A 100(14):8490–8495. https://doi.org/10.1073/pnas.1432843100
Liang Y, Ganem D (2004) RBP-J (CSL) is essential for activation of the K14/vGPCR promoter of Kaposi’s sarcoma-associated herpesvirus by the lytic switch protein RTA. J Virol 78(13):6818–6826. https://doi.org/10.1128/jvi.78.13.6818-6826.2004
Lin H-R, Ganem D (2011) Viral microRNA target allows insight into the role of translation in governing microRNA target accessibility. Proc Natl Acad Sci U S A 108(13):5148–5153. https://doi.org/10.1073/pnas.1102033108
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(7):800–811. https://doi.org/10.1038/sj.onc.1204163
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(1):e16224. https://doi.org/10.1371/journal.pone.0016224
Lin YT, Kincaid RP, Arasappan D, Dowd SE, Hunicke-Smith SP, Sullivan CS (2010) Small RNA profiling reveals antisense transcription throughout the KSHV genome and novel small RNAs. RNA 16(8):1540–1558. https://doi.org/10.1261/rna.1967910
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(9):4722–4731. https://doi.org/10.1128/jvi.02548-06
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(19):10451–10459. https://doi.org/10.1128/jvi.00804-07
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(16):13745–13751. https://doi.org/10.1074/jbc.M110480200
Loh J, Huang Q, Petros AM, Nettesheim D, van Dyk LF, Labrada L, Speck SH, Levine B, Olejniczak ET, Virgin HWIV (2005) A surface groove essential for viral Bcl-2 function during chronic infection in vivo. PLoS Pathog 1(1):e10. https://doi.org/10.1371/journal.ppat.0010010
Lu CC, Li Z, Chu CY, Feng J, Feng J, Sun R, Rana TM (2010a) MicroRNAs encoded by Kaposi’s sarcoma-associated herpesvirus regulate viral life cycle. EMBO Rep 11(10):784–790. https://doi.org/10.1038/embor.2010.132
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(6):2697–2706. https://doi.org/10.1128/jvi.01997-09
Lu J, Verma SC, Cai Q, Robertson ES (2011) The single RBP-Jkappa site within the LANA promoter is crucial for establishing Kaposi’s sarcoma-associated herpesvirus latency during primary infection. J Virol 85(13):6148–6161. https://doi.org/10.1128/jvi.02608-10
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(44):31944–31953. https://doi.org/10.1074/jbc.M706430200
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(17):8194–8201
Mahotka C, Wenzel M, Springer E, Gabbert HE, Gerharz CD (1999) Survivin-deltaEx3 and survivin-2B: two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties. Cancer Res 59(24):6097–6102
Mann DJ, Child ES, Swanton C, Laman H, Jones N (1999) Modulation of p27(Kip1) levels by the cyclin encoded by Kaposi’s sarcoma-associated herpesvirus. EMBO J 18(3):654–663. https://doi.org/10.1093/emboj/18.3.654
Matsumoto A, Onoyama I, Sunabori T, Kageyama R, Okano H, Nakayama KI (2011) Fbxw7-dependent degradation of Notch is required for control of “stemness” and neuronal-glial differentiation in neural stem cells. J Biol Chem 286(15):13754–13764. https://doi.org/10.1074/jbc.M110.194936
McClure LV, Kincaid RP, Burke JM, Grundhoff A, Sullivan CS (2013) Comprehensive mapping and analysis of Kaposi’s sarcoma-associated herpesvirus 3′ UTRs identify differential posttranscriptional control of gene expression in lytic versus latent infection. J Virol 87(23):12838–12849. https://doi.org/10.1128/jvi.02374-13
McCormick C, Ganem D (2005) The kaposin B protein of KSHV activates the p38/MK2 pathway and stabilizes cytokine mRNAs. Science (New York, NY) 307(5710):739–741. https://doi.org/10.1126/science.1105779
McCormick C, Ganem D (2006) Phosphorylation and function of the kaposin B direct repeats of Kaposi’s sarcoma-associated herpesvirus. J Virol 80(12):6165–6170. https://doi.org/10.1128/jvi.02331-05
Montaner S, Sodhi A, Pece S, Mesri EA, Gutkind JS (2001) The Kaposi’s sarcoma-associated herpesvirus G protein-coupled receptor promotes endothelial cell survival through the activation of Akt/protein kinase B. Cancer Res 61(6):2641–2648
Moody R, Zhu Y, Huang Y, Cui X, Jones T, Bedolla R, Lei X, Bai Z, Gao SJ (2013) KSHV microRNAs mediate cellular transformation and tumorigenesis by redundantly targeting cell growth and survival pathways. PLoS Pathog 9(12):e1003857. https://doi.org/10.1371/journal.ppat.1003857
Moore PS, Boshoff C, Weiss RA, Chang Y (1996a) Molecular mimicry of human cytokine and cytokine response pathway genes by KSHV. Science (New York, NY) 274(5293):1739–1744
Moore PS, Chang Y (1998) Antiviral activity of tumor-suppressor pathways: clues from molecular piracy by KSHV. Trends in genetics : TIG 14(4):144–150
Moore PS, Gao SJ, Dominguez G, Cesarman E, Lungu O, Knowles DM, Garber R, Pellett PE, McGeoch DJ, Chang Y (1996b) Primary characterization of a herpesvirus agent associated with Kaposi’s sarcomae. J Virol 70(1):549–558
Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, Kinzler KW (1997) Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science (NY) 275(5307):1787–1790
Morris VA, Punjabi AS, Lagunoff M (2008) Activation of Akt through gp130 receptor signaling is required for Kaposi’s sarcoma-associated herpesvirus-induced lymphatic reprogramming of endothelial cells. J Virol 82(17):8771–8779. https://doi.org/10.1128/JVI.00766-08
Morris VA, Punjabi AS, Wells RC, Wittkopp CJ, Vart R, Lagunoff M (2012) The KSHV viral IL-6 homolog is sufficient to induce blood to lymphatic endothelial cell differentiation. Virology 428(2):112–120. https://doi.org/10.1016/j.virol.2012.03.013
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(6):4980–4988
Mutocheluh M, Hindle L, Areste C, Chanas SA, Butler LM, Lowry K, Shah K, Evans DJ, Blackbourn DJ (2011) Kaposi’s sarcoma-associated herpesvirus viral interferon regulatory factor-2 inhibits type 1 interferon signalling by targeting interferon-stimulated gene factor-3. J Gen Virol 92(Pt 10):2394–2398. https://doi.org/10.1099/vir.0.034322-0
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(4):376–385. https://doi.org/10.1016/j.chom.2009.03.003
Nakamura H, Li M, Zarycki J, Jung JU (2001) Inhibition of p53 tumor suppressor by viral interferon regulatory factor. J Virol 75(16):7572–7582. https://doi.org/10.1128/jvi.75.16.7572-7582.2001
Nakayama KI, Nakayama K (2006) Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer 6(5):369–381. https://doi.org/10.1038/nrc1881
Naranatt PP, Akula SM, Zien CA, Krishnan HH, Chandran B (2003) Kaposi’s sarcoma-associated herpesvirus induces the phosphatidylinositol 3-Kinase-PKC-ζ-MEK-ERK signaling pathway in target cells early during infection: implications for infectivity. J Virol 77(2):1524–1539. https://doi.org/10.1128/JVI.77.2.1524-1539.2003
Nayar U, Lu P, Goldstein RL, Vider J, Ballon G, Rodina A, Taldone T, Erdjument-Bromage H, Chomet M, Blasberg R, Melnick A, Cerchietti L, Chiosis G, Wang YL, Cesarman E (2013) Targeting the Hsp90-associated viral oncoproteome in gammaherpesvirus-associated malignancies. Blood 122(16):2837–2847. https://doi.org/10.1182/blood-2013-01-479972
Ojala PM, Yamamoto K, Castanos-Velez E, Biberfeld P, Korsmeyer SJ, Makela TP (2000) The apoptotic v-cyclin-CDK6 complex phosphorylates and inactivates Bcl-2. Nat Cell Biol 2(11):819–825. https://doi.org/10.1038/35041064
Osborne J, Moore PS, Chang Y (1999) KSHV-encoded viral IL-6 activates multiple human IL-6 signaling pathways. Hum Immunol 60(10):921–927
Pan H, Xie J, Ye F, Gao SJ (2006) Modulation of Kaposi’s sarcoma-associated herpesvirus infection and replication by MEK/ERK, JNK, and p38 multiple mitogen-activated protein kinase pathways during primary infection. J Virol 80(11):5371–5382. https://doi.org/10.1128/JVI.02299-05
Parravicini C, Chandran B, Corbellino M, Berti E, Paulli M, Moore PS, Chang Y (2000) Differential viral protein expression in Kaposi’s sarcoma-associated herpesvirus-infected diseases: Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. Am J Pathol 156(3):743–749. https://doi.org/10.1016/S0002-9440(10)64940-1
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(18):8660–8673
Pati S, Foulke JS Jr, Barabitskaya O, Kim J, Nair BC, Hone D, Smart J, Feldman RA, Reitz M (2003) Human herpesvirus 8-encoded vGPCR activates nuclear factor of activated T cells and collaborates with human immunodeficiency virus type 1 Tat. J Virol 77(10):5759–5773
Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH (2001) Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 22(2):153–183. https://doi.org/10.1210/edrv.22.2.0428
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(4):269–276. https://doi.org/10.1038/nmeth746
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(16):8231–8240. https://doi.org/10.1128/jvi.01696-09
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(12):926–935
Qin Z, Kearney P, Plaisance K, Parsons CH (2010) Pivotal advance: Kaposi’s sarcoma-associated herpesvirus (KSHV)-encoded microRNA specifically induce IL-6 and IL-10 secretion by macrophages and monocytes. J Leukoc Biol 87(1):25–34
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(10):1121–1127. https://doi.org/10.1038/80459
Reed JC (1997) Bcl-2 family proteins: regulators of apoptosis and chemoresistance in hematologic malignancies. Semin Hematol 34(4 Suppl 5):9–19
Rossetto CC, Pari G (2012) KSHV PAN RNA associates with demethylases UTX and JMJD3 to activate lytic replication through a physical interaction with the virus genome. PLoS Pathog 8(5):e1002680. https://doi.org/10.1371/journal.ppat.1002680
Rossetto CC, Pari GS (2011) Kaposi’s sarcoma-associated herpesvirus noncoding polyadenylated nuclear RNA interacts with virus- and host cell-encoded proteins and suppresses expression of genes involved in immune modulation. J Virol 85(24):13290–13297. https://doi.org/10.1128/jvi.05886-11
Rossetto CC, Tarrant-Elorza M, Verma S, Purushothaman P, Pari GS (2013) Regulation of viral and cellular gene expression by Kaposi’s sarcoma-associated herpesvirus polyadenylated nuclear RNA. J Virol 87(10):5540–5553. https://doi.org/10.1128/jvi.03111-12
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(25):14862–14867
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(7):5722–5730
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(14):9301–9305. https://doi.org/10.1128/jvi.79.14.9301-9305.2005
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 Pathog 3(5):e65. https://doi.org/10.1371/journal.ppat.0030065
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(1):505–513
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(13):6193–6198. https://doi.org/10.1128/jvi.75.13.6193-6198.2001
Sharma-Walia N, Krishnan HH, Naranatt PP, Zeng L, Smith MS, Chandran B (2005) ERK1/2 and MEK1/2 induced by Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) early during infection of target cells are essential for expression of viral genes and for establishment of infection. J Virol 79(16):10308–10329. https://doi.org/10.1128/JVI.79.16.10308-10329.2005
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(5):2257–2266. https://doi.org/10.1128/JVI.80.5.2257-2266.2006
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(23):12836–12845. https://doi.org/10.1128/jvi.01804-07
Staskus KA, Sun R, Miller G, Racz P, Jaslowski A, Metroka C, Brett-Smith H, Haase AT (1999) Cellular tropism and viral interleukin-6 expression distinguish human herpesvirus 8 involvement in Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. J Virol 73(5):4181–4187
Strahan R, Uppal T, Verma SC (2016) Next-generation sequencing in the understanding of Kaposi’s sarcoma-associated herpesvirus (KSHV) biology. Viruses 8(4):92. https://doi.org/10.3390/v8040092
Su LK, Vogelstein B, Kinzler KW (1993) Association of the APC tumor suppressor protein with catenins. Sci (NY) 262(5140):1734–1737
Sun R, Lin SF, Gradoville L, Miller G (1996) Polyadenylylated nuclear RNA encoded by Kaposi sarcoma-associated herpesvirus. Proc Natl Acad Sci USA 93(21):11883–11888
Swanton C, Mann DJ, Fleckenstein B, Neipel F, Peters G, Jones N (1997) Herpes viral cyclin/Cdk6 complexes evade inhibition by CDK inhibitor proteins. Nature 390(6656):184–187. https://doi.org/10.1038/36606
Tamura T, Yanai H, Savitsky D, Taniguchi T (2008) The IRF family transcription factors in immunity and oncogenesis. Annu Rev Immunol 26:535–584. https://doi.org/10.1146/annurev.immunol.26.021607.090400
Taniguchi T, Takaoka A (2002) The interferon-alpha/beta system in antiviral responses: a multimodal machinery of gene regulation by the IRF family of transcription factors. Curr Opin Immunol 14(1):111–116
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(6624):517–521. https://doi.org/10.1038/386517a0
Tomlinson CC, Damania B (2004) The K1 protein of Kaposi’s sarcoma-associated herpesvirus activates the Akt signaling pathway. J Virol 78(4):1918–1927
Wang FZ, Akula SM, Pramod NP, Zeng L, Chandran B (2001) Human herpesvirus 8 envelope glycoprotein K8.1A interaction with the target cells involves heparan sulfate. J Virol 75(16):7517–7527. https://doi.org/10.1128/JVI.75.16.7517-7527.2001
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(11):2602–2615. https://doi.org/10.1093/emboj/21.11.2602
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(7):687–693. https://doi.org/10.1038/ng1384
Wang KC, Chang HY (2011) Molecular mechanisms of long noncoding RNAs. Mol Cell 43(6):904–914. https://doi.org/10.1016/j.molcel.2011.08.018
Webster MT, Rozycka M, Sara E, Davis E, Smalley M, Young N, Dale TC, Wooster R (2000) Sequence variants of the axin gene in breast, colon, and other cancers: an analysis of mutations that interfere with GSK3 binding. Genes Chromosom Cancer 28(4):443–453
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(13):8525–8538. https://doi.org/10.1074/jbc.M809252200
Xie J, Ajibade AO, Ye F, Kuhne K, Gao SJ (2008) Reactivation of Kaposi’s sarcoma-associated herpesvirus from latency requires MEK/ERK, JNK and p38 multiple mitogen-activated protein kinase pathways. Virology 371(1):139–154. https://doi.org/10.1016/j.virol.2007.09.040
Xie J, Pan H, Yoo S, Gao SJ (2005) Kaposi’s sarcoma-associated herpesvirus induction of AP-1 and interleukin 6 during primary infection mediated by multiple mitogen-activated protein kinase pathways. J Virol 79(24):15027–15037. https://doi.org/10.1128/jvi.79.24.15027-15037.2005
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(8):e1001046. https://doi.org/10.1371/journal.ppat.1001046
Yu Y, Hayward GS (2010) The ubiquitin E3 ligase RAUL negatively regulates type i interferon through ubiquitination of the transcription factors IRF7 and IRF3. Immunity 33(6):863–877. https://doi.org/10.1016/j.immuni.2010.11.027
Yu Y, Wang SE, Hayward GS (2005) The KSHV immediate-early transcription factor RTA encodes ubiquitin E3 ligase activity that targets IRF7 for proteosome-mediated degradation. Immunity 22(1):59–70. https://doi.org/10.1016/j.immuni.2004.11.011
Zhong W, Ganem D (1997) Characterization of ribonucleoprotein complexes containing an abundant polyadenylated nuclear RNA encoded by Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8). J Virol 71(2):1207–1212
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(13):6641–6646
Zhu FX, King SM, Smith EJ, Levy DE, Yuan Y (2002) A Kaposi’s sarcoma-associated herpesviral protein inhibits virus-mediated induction of type I interferon by blocking IRF-7 phosphorylation and nuclear accumulation. Proc Natl Acad Sci U S A 99(8):5573–5578. https://doi.org/10.1073/pnas.082420599
Zhu Y, Huang Y, Jung JU, Lu C, Gao S-J (2014) Viral miRNA targeting of bicistronic and polycistronic transcripts. Current opinion in virology 0:66–72. https://doi.org/10.1016/j.coviro.2014.04.004
Ziegelbauer JM, Sullivan CS, Ganem D (2009) Tandem array-based expression screens identify host mRNA targets of virus-encoded microRNAs. Nat Genet 41(1):130–134. https://doi.org/10.1038/ng.266
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(1):701–707
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Watanabe, T., Sugimoto, A., Hosokawa, K., Fujimuro, M. (2018). Signal Transduction Pathways Associated with KSHV-Related Tumors. In: Kawaguchi, Y., Mori, Y., Kimura, H. (eds) Human Herpesviruses. Advances in Experimental Medicine and Biology, vol 1045. Springer, Singapore. https://doi.org/10.1007/978-981-10-7230-7_15
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Print ISBN: 978-981-10-7229-1
Online ISBN: 978-981-10-7230-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)