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30 - KSHV manipulation of the cell cycle and programmed cell death pathways

from Part II - Basic virology and viral gene effects on host cell functions: gammaherpesviruses

Published online by Cambridge University Press:  24 December 2009

By
Patrick S. Moore
Edited by
Ann Arvin ,
Gabriella Campadelli-Fiume ,
Edward Mocarski ,
Patrick S. Moore ,
Bernard Roizman ,
Richard Whitley  and
Koichi Yamanishi
Patrick S. Moore
Affiliation:
Molecular Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA USA
Ann Arvin
Affiliation:
Stanford University, California
Gabriella Campadelli-Fiume
Affiliation:
Università degli Studi, Bologna, Italy
Edward Mocarski
Affiliation:
Emory University, Atlanta
Patrick S. Moore
Affiliation:
University of Pittsburgh
Bernard Roizman
Affiliation:
University of Chicago
Richard Whitley
Affiliation:
University of Alabama, Birmingham
Koichi Yamanishi
Affiliation:
University of Osaka, Japan
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Summary

Disruptions of cell cycle and apoptotic regulatory control are primary hallmarks tumor cells. It is therefore not surprising that Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8), a tumor virus, encodes viral proteins targeting these cell growth regulation mechanisms. The extent and range of KSHV genes devoted to manipulating these processes is, however, remarkable.

As described in previous chapters, herpesviral structural and replication-related genes are highly conserved among the herpesviruses, including KSHV. In contrast, regulatory genes generating proteins that modify the cellular environment – particularly during latency – are generally unique to each virus. As will become evident in this chapter, even though KSHV and EBV are closely related to each other, there are few sequence homologies among the oncogenes and non-structural regulatory genes found in the two viruses. Despite this, there is a striking functional similarity between the two viruses (Table 30.1). EBV encodes multiple highly evolved transcription factors and signaling proteins that induce many of the same cellular genes that KSHV has pirated into its genome. Further, once herpesvirus targeting of a cellular pathway has been found for one herpesvirus (e.g., HSV-1 downregulation of MHC I surface expression, Hill et al., 1994), searching for functional similarities among other herpesviruses has been particularly rewarding (e.g., Coscoy et al., 2000). It is therefore not surprising that KSHV and EBV share pathways for cell transformation although they achieve this through very different mechanisms.

Type
Chapter
Information
Human Herpesviruses
Biology, Therapy, and Immunoprophylaxis
 , pp. 540 - 558
Publisher: Cambridge University Press
Print publication year: 2007

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References

Bais, C., Santomasso, B., Coso, O.et al. (1998). G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator. Nature, 391(6662), 86–89.CrossRefGoogle ScholarPubMed
Bakhshi, A., Jensen, J. P., Goldman, P.et al. (1985). Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell, 41(3), 899–906.CrossRefGoogle Scholar
Banin, S., Moyal, L., Shieh, S.et al. (1998). Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science, 281(5383), 1674–1677.CrossRefGoogle ScholarPubMed
Barozzi, P., Luppi, M., Facchetti, F.et al. (2003). Post-transplant Kaposi sarcoma originates from the seeding of donor-derived progenitors. Nat. Med., 9(5), 554–561.CrossRefGoogle ScholarPubMed
Bellows, D. S., Chau, B. N., Lee, P., Lazebnik, Y., Burns, W. H., and Hardwick, J. M. (2000). Antiapoptotic herpesvirus bcl-2 homologs escape caspase-mediated conversion to proapoptotic proteins. J. Virol., 74(11), 5024–5031.CrossRefGoogle ScholarPubMed
Benedict, C. A., Norris, P. S., and Ware, C. F. (2002). To kill or be killed: viral evasion of apoptosis. Nat. Immunol., 3(11), 1013–1018.CrossRefGoogle ScholarPubMed
Bieleski, L., Hindley, C., and Talbot, S. J. (2004). A polypyrimidine tract facilitates the expression of Kaposi's sarcoma-associated herpesvirus vFLIP through an internal ribosome entry site. J. Gen. Virol., 85(3), 615–620.CrossRefGoogle ScholarPubMed
Bieleski, L. and Talbot, S. J. (2001). Kaposi's sarcoma-associated herpesvirus vCyclin open reading frame contains an internal ribosome entry site. J. Virol., 75(4), 1864–1869.CrossRefGoogle ScholarPubMed
Borah, S., Verma, S. C., and Robertson, E. S. (2004). ORF73 of Herpesvirus saimiri, a viral homolog of Kaposi's sarcoma-associated herpesvirus, modulates the two cellular tumor suppressor proteins p53 and pRb. J. Virol., 78(19), 10336–10347.CrossRefGoogle ScholarPubMed
Boshoff, C., Endo, Y., Collins, P. D.et al. (1997). Angiogenic and HIV inhibitory functions of KSHV-encoded chemokines. Science, 278, 290–294.CrossRefGoogle ScholarPubMed
Braithwaite, A. W. and Russell, I. A. (2001). Induction of cell death by adenoviruses. Apoptosis, 6(5), 359–370.CrossRefGoogle ScholarPubMed
Burger, R., Neipel, F., Fleckenstein, B.et al. (1998). Human herpesvirus type 8 interleukin-6 homologue is functionally active on human myeloma cells. Blood, 91(6), 1858–1863.Google ScholarPubMed
Cai, X. and Cullen, B. R. (2006). Transcriptional origin of Kaposi's sarcoma-associated herpesvirus microRNAs, J. Virol., 80(5), 2234–2242.CrossRefGoogle ScholarPubMed
Cai, X., Lu, S., Zhang, Z., Gonzalez, C. M., Damania, B., and Cullen, B. R. (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.CrossRefGoogle ScholarPubMed
Cannon, M., Philpott, N. J., and 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(1), 57–67.CrossRefGoogle ScholarPubMed
Cesarman, E., Nador, R. G., Bai, F.et al. (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.Google ScholarPubMed
Cesarman, E., Mesri, E. A., and Gershengorn, M. C. (2000). Viral G protein-coupled receptor and Kaposi's sarcoma: a model of paracrine neoplasia? [comment]. J. Exp. Med., 191(3), 417–422.CrossRefGoogle Scholar
Chang, Y., Moore, P. S., Talbot, S. J.et al. (1996). Cyclin encoded by KS herpesvirus. Nature, 382, 410.Google Scholar
Chatterjee, M., Osborne, J., Bestetti, G., Chang, Y., and Moore, P. S. (2002). Viral IL-6-induced cell proliferation and immune evasion of interferon activity. Science, 298(5597), 1432–1435.CrossRefGoogle ScholarPubMed
Chaudhary, P. M., Jasmin, A., Eby, M. T., and Hood, L. (1999). Modulation of the NF-kappa B pathway by virally encoded death effector domains-containing proteins. Oncogene, 18(42), 5738–5746.CrossRefGoogle ScholarPubMed
Cheng, E. H., Nicholas, J., Bellows, D. S.et al. (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. USA, 94(2), 690–694.CrossRefGoogle ScholarPubMed
Cheng, E. H., Wei, M. C., Weiler, S.et al. (2001). BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol. Cell, 8(3), 705–711.CrossRefGoogle ScholarPubMed
Child, E. S. and Mann, D. J. (2001). Novel properties of the cyclin encoded by Human Herpesvirus 8 that facilitate exit from quiescence, Oncogene, 20(26), 3311–3322.CrossRefGoogle ScholarPubMed
Chiou, C. J., Poole, L. J., Kim, P. S.et al. (2002). Patterns of gene expression and a transactivation function exhibited by the vGCR (ORF74) chemokine receptor protein of Kaposi's sarcoma-associated herpesvirus. J. Virol., 76(7), 3421–3439.CrossRefGoogle Scholar
Chow, D.-C., He, X.-L., Snow, A. L., Rose-John, S., and Garcia, K. C. (2001). Structure of an extracellular gp130 cytokine receptor signaling complex. Science, 291(5511), 2150–2155.CrossRefGoogle ScholarPubMed
Coscoy, L. and Ganem, D. (2000). Kaposi's sarcoma-associated herpesvirus encodes two proteins that block cell surface display of MHC class I chains by enhancing their endocytosis. Proc. Natl Acad. Sci. USA, 97(14), 8051–8056.CrossRefGoogle ScholarPubMed
Cuconati, A. and White, E. (2002). Viral homologs of BCL-2: role of apoptosis in the regulation of virus infection. Genes Dev., 16(19), 2465–2478.CrossRefGoogle ScholarPubMed
Dairaghi, D. J., Fan, R. A., McMaster, B. E., Hanley, M. R., and Schall, T. J. (1999). HHV8-encoded vMIP-I selectively engages chemokine receptor CCR8. Agonist and antagonist profiles of viral chemokines. J. Biol. Chem., 274(31), 21569–21574.CrossRefGoogle ScholarPubMed
Damania, B., Choi, J. K., and Jung, J. U. (2000). Signaling activities of gammaherpesvirus membrane proteins. J. Virol., 74(4), 1593–1601.CrossRefGoogle ScholarPubMed
Danial, N. N. and Korsmeyer, S. J. (2004). Cell death: critical control points, Cell, 116(2), 205–219.CrossRefGoogle ScholarPubMed
de Stanchina, E., McCurrach, M. E., Zindy, F.et al. (1998). E1A signaling to p53 involves the p19(ARF) tumor suppressor, Genes Dev., 12(15), 2434–2442.CrossRefGoogle ScholarPubMed
Debbas, M. and White, E. (1993). Wild-type p53 mediates apoptosis by E1A, which is inhibited by E1B. Genes Dev., 7, 546–554.CrossRefGoogle ScholarPubMed
Djerbi, M., Screpanti, V., Catrina, A. I., Bogen, B., Biberfeld, P., and Grandien, A. (1999). The inhibitor of death receptor signaling, FLICE-inhibitory protein defines a new class of tumor progression factors, J. Exp. Med., 190(7), 1025–1032.CrossRefGoogle ScholarPubMed
Ellis, M., Chew, Y. P., Fallis, L.et al. (1999). Degradation of p27(Kip) cdk inhibitor triggered by Kaposi's sarcoma virus cyclin-cdk6 complex, EMBO J., 18(3), 644–653.CrossRefGoogle ScholarPubMed
Endres, M. J., Garlisi, C. G., Xiao, H., Shan, L., and Hedrick, J. A. (1999). The Kaposi's sarcoma-related herpesvirus (KSHV)-encoded chemokine vMIP- I is a specific agonist for the CC chemokine receptor (CCR)8. J. Exp. Med., 189(12), 1993–1998.CrossRefGoogle ScholarPubMed
Feng, P., Park, J., Lee, B. S., Lee, S. H., Bram, R. J., and Jung, J. U. (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.CrossRefGoogle ScholarPubMed
Feng, P., Scott, C. W., Cho, N. H.et al. (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.CrossRefGoogle ScholarPubMed
Field, N., Low, W., Daniels, M.et al. (2003). KSHV vFLIP binds to IKK-gamma to activate IKK, J. Cell. Sci., 116(18), 3721–3728.CrossRefGoogle ScholarPubMed
Fraser, A. and James, C. (1998). Fermenting debate: do yeast undergo apoptosis?Trends Cell. Biol., 8(6), 219–221.CrossRefGoogle ScholarPubMed
Friborg, J. Jr., Kong, W., Hottiger, M. O., and Nabel, G. J. (1999). p53 inhibition by the LANA protein of KSHV protects against cell death. Nature, 402(6764), 889–894.CrossRefGoogle ScholarPubMed
Fujimuro, M. and Hayward, S. D. (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.CrossRefGoogle ScholarPubMed
Fujimuro, M., Wu, F. Y., ApRhys, C.et al. (2003). A novel viral mechanism for dysregulation of beta-catenin in Kaposi's sarcoma-associated herpesvirus latency. Nat. Med., 9(3), 300–306.CrossRefGoogle ScholarPubMed
Gao, S.-J., Boshoff, C., Jayachandra, S., Weiss, R. A., Chang, Y., and Moore, P. S. (1997). KSHV ORF K9 (vIRF) is an oncogene that inhibits the interferon signaling pathway. Oncogene, 15, 1979–1986.CrossRefGoogle ScholarPubMed
Glaunsinger, B. and Ganem, D. (2004). Lytic KSHV infection inhibits host gene expression by accelerating global mRNA turnover. Mol. Cell., 13(5), 713–723.CrossRefGoogle ScholarPubMed
Godden-Kent, D., Talbot, S. J., Boshoff, C.et al. (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.Google Scholar
Gorospe, M., Cirielli, C., Wang, X., Seth, P., Capogrossi, M. C., and Holbrook, N. J. (1997). p21(Waf1/Cip1) protects against p53-mediated apoptosis of human melanoma cells. Oncogene, 14(8), 929–935.CrossRefGoogle ScholarPubMed
Gruffat, H., Portes-Sentis, S., Sergeant, A., and Manet, E. (1999). Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) encodes a homologue of the Epstein–Barr virus bZip protein EB1. J. Gen. Virol., 80(3), 557–561.CrossRefGoogle ScholarPubMed
Grundhoff, A. and Ganem, D. (2001). Mechanisms governing expression of the v-FLIP gene of Kaposi's sarcoma-associated herpesvirus. J. Virol., 75(4), 1857–1863.CrossRefGoogle ScholarPubMed
Guasparri, I., Keller, S. A., and Cesarman, E. (2004). KSHV vFLIP is essential for the survival of infected lymphoma cells. J. Exp. Med., 199(7), 993–1003.CrossRefGoogle ScholarPubMed
Guo, H. G., Sadowska, M., Reid, W., Tschachler, E., Hayward, G., and Reitz, M. (2003). Kaposi's sarcoma-like tumors in a human herpesvirus 8 ORF74 transgenic mouse. J. Virol., 77(4), 2631–2639.CrossRefGoogle Scholar
Gwack, Y., Byun, H., Hwang, S., Lim, C., and Choe, J. (2001a). CREB-binding protein and histone deacetylase regulate the transcriptional activity of Kaposi's sarcoma-associated herpesvirus open reading frame 50. J. Virol., 75(4) 1909–1917.CrossRefGoogle Scholar
Gwack, Y., Hwang, S., Byun, H.et al. (2001b). Kaposi's sarcoma-associated herpesvirus open reading frame 50 represses p53-induced transcriptional activity and apoptosis. J. Virol., 75(13), 6245–6248.CrossRefGoogle Scholar
Hayward, S. D., Liu, J., and Fujimuro, M. (2006). Notch and Wnt signaling: mimicry and manipulation by gamma herpesviruses, Sci. STKE, 2006(335), re4.Google ScholarPubMed
Hobeika, A. C., Subramaniam, P. S., and Johnson, H. M. (1997). IFNα induces the expression of the cyclin-dependent kinase inhibitor p21 in human prostate cancer cells. Oncogene, 14(10), 1165–1170.CrossRefGoogle ScholarPubMed
Holst, P. J., Rosenkilde, M. M., Manfra, D.et al. (2001). Tumorigenesis induced by the HHV8-encoded chemokine receptor requires ligand modulation of high constitutive activity. J. Clin. Invest., 108(12), 1789–1796.CrossRefGoogle ScholarPubMed
Huang, Q., Petros, A. M., Virgin, H. W., Fesik, S. W., and Olejniczak, E. T. (2002). Solution structure of a Bcl-2 homolog from Kaposi sarcoma virus. Proc. Natl Acad. Sci. USA, 99(6), 3428–3433.CrossRefGoogle ScholarPubMed
Hwang, S., Gwack, Y., Byun, H., Lim, C., and Choe, J. (2001). The Kaposi's sarcoma-associated herpesvirus K8 protein interacts with CREB-binding protein (CBP) and represses CBP-mediated transcription. J. Virol., 75(19), 9509–9516.CrossRefGoogle ScholarPubMed
Izumiya, Y., Lin, S. F., Ellison, T. J.et al. (2003). Cell cycle regulation by Kaposi's sarcoma-associated herpesvirus K-bZIP: direct interaction with cyclin-CDK2 and induction of G1 growth arrest. J. Virol., 77(17), 9652–9661.CrossRefGoogle ScholarPubMed
Jeffrey, P. D., Tong, L., and Pavletich, N. P. (2000). Structural basis of inhibition of CDK–cyclin complexes by INK4 inhibitors. Genes Dev., 14(24), 3115–3125.CrossRefGoogle ScholarPubMed
Jeong, J. H., Orvis, J., Kim, J. W., McMurtrey, C. P., Renne, R., and Dittmer, D. P. (2004). Regulation and autoregulation of the promoter for the latency-associated nuclear antigen of Kaposi's Sarcoma-associated herpesvirus. J. Biol. chem., 279, 16822–16831.CrossRefGoogle ScholarPubMed
Jones, K. D., Aoki, Y., Chang, Y., Moore, P. S., Yarchoan, R., and 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(8), 2871–2879.Google ScholarPubMed
Judde, J. G., Lacoste, V., Briere, J.et al. (2000). Monoclonality or oligoclonality of human herpesvirus 8 terminal repeat sequences in Kaposi's sarcoma and other diseases. J. Natl Cancer Inst., 92(9), 729–736.CrossRefGoogle ScholarPubMed
Kaldis, P., Ojala, P. M., Tong, L., Makela, T. P., and Solomon, M. J. (2001). CAK-independent activation of CDK6 by a viral cyclin, Mol. Biol. Cell, 12(12), 3987–3999.CrossRefGoogle ScholarPubMed
Katano, H., Ogawa-Goto, K., Hasegawa, H., Kurata, T., and Sata, T. (2001a). Human-herpesvirus-8-encoded K8 protein colocalizes with the promyelocytic leukemia protein (PML) bodies and recruits p53 to the PML bodies. Virology, 286(2), 446–455.CrossRefGoogle Scholar
Katano, H., Sato, Y., and Sata, T. (2001b). Expression of p53 and human herpesvirus-8 (HHV-8)-encoded latency-associated nuclear antigen with inhibition of apoptosis in HHV-8-associated malignancies. Cancer, 92(12), 3076–3084.3.0.CO;2-D>CrossRefGoogle Scholar
Keller, S. A., Schattner, E. J., and Cesarman, E. (2000). Inhibition of NF-kappa B induces apoptosis of KSHV-infected primary effusion lymphoma cells. Blood, 96(7), 2537–2542.Google ScholarPubMed
Kirshner, J. R., Staskus, K., Haase, A., Lagunoff, M., and Ganem, D. (1999). Expression of the open reading frame 74 (G-protein-coupled receptor) gene of Kaposi's sarcoma (KS)-associated herpesvirus: implications for KS pathogenesis. J. Virol., 73(7), 6006–6014.Google ScholarPubMed
Klotzbucher, A., Stewart, E., Harrison, D., and Hunt, T. (1996). The ‘destruction box’ of cyclin A allows B-type cyclins to be ubiquitinated, but not efficiently destroyed. EMBO J., 15(12), 3053–3064.Google Scholar
Kozar, K., Ciemerych, M. A., Rebel, V. I.et al. (2004). Mouse development and cell proliferation in the absence of D-cyclins. Cell, 118(4), 477–491.CrossRefGoogle ScholarPubMed
Krishnan, H. H., Naranatt, P. P., Smith, M. S., Zeng, L., Bloomer, C., and Chandran, B. (2004). Concurrent expression of latent and a limited number of lytic genes with immune modulation and antiapoptotic function by Kaposi's sarcoma-associated herpesvirus early during infection of primary endothelial and fibroblast cells and subsequent decline of lytic gene expression. J. Virol., 78(7), 3601–3620.CrossRefGoogle Scholar
Krueger, A., Baumann, S., Krammer, P. H., and Kirchhoff, S. (2001). FLICE-inhibitory proteins: Regulators of death receptor-mediated apoptosis. Mol. Biol. Cell, 21(24), 8247–8254.CrossRefGoogle ScholarPubMed
Lagunoff, M. and Carroll, P. A. (2003). Inhibition of apoptosis by the gamma-herpesviruses. Int. Rev. Immunol., 22(5–6), 373–399.CrossRefGoogle ScholarPubMed
Lagunoff, M., Majeti, R., Weiss, A., and Ganem, D. (1999). Deregulated signal transduction by the K1 gene product of Kaposi's sarcoma-associated herpesvirus. Proc. Natl Acad. Sci. USA, 96(10), 5704–5709.CrossRefGoogle ScholarPubMed
Lagunoff, M., Lukac, D. M., and 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(13), 5891–5898.CrossRefGoogle ScholarPubMed
Laman, H., Coverley, D., Krude, T., Laskey, R., and Jones, N. (2001). Viral cyclin-cyclin-dependent kinase 6 complexes initiate nuclear DNA replication. Mol. Cell Biol., 21(2), 624–635.CrossRefGoogle ScholarPubMed
Lan, K., Choudhuri, T., Murakami, M., Kuppers, D. A., and Robertson, E. S. (2006). Intracellular activated Notch1 is critical for proliferation of Kaposi's sarcoma-associated herpesvirus-associated B-lymphoma cell lines in vitro, J. Virol., 80(13), 6411–6419.CrossRefGoogle ScholarPubMed
Lane, D. P. (1992). p53, guardian of the genome. Nature, 358(6381), 15–16.CrossRefGoogle ScholarPubMed
Lee, B. S., Alvarez, X., Ishido, S., Lackner, A. A., and Jung, J. U. (2000). Inhibition of intracellular transport of B cell antigen receptor complexes by Kaposi's sarcoma-associated herpesvirus K1. J. Exp. Med., 192(1), 11–21.CrossRefGoogle ScholarPubMed
Lee, B. S., Connole, M., Tang, Z., Harris, N. L., and Jung, J. U. (2003). Structural analysis of the Kaposi's sarcoma-associated herpesvirus K1 protein. J. Virol., 77(14), 8072–8086.CrossRefGoogle ScholarPubMed
Lee, H., Guo, J., Li, M.et al. (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.CrossRefGoogle Scholar
Lee, H., Veazey, R., Williams, K.et al. (1998b). Deregulation of cell growth by the K1 gene of Kaposi's sarcoma-associated herpesvirus. Nat. Med., 4(4), 435–440.CrossRefGoogle Scholar
Lee, J. H. and Paull, T. T. (2004). Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science, 304.(5667), 93–96.CrossRefGoogle ScholarPubMed
Li, M., Lee, H., Yoon, D. W.et al. (1997). Kaposi's sarcoma-associated herpesvirus encodes a functional cyclin. J. Virol., 71(3), 1984–1991.Google ScholarPubMed
Li, M., Damania, B., Alvarez, X., Ogryzko, V., Ozato, K., and Jung, J. U. (2000). Inhibition of p300 histone acetyltransferase by viral interferon regulatory factor. Mol. Cell. Biol., 20(21), 8254–8263.CrossRefGoogle ScholarPubMed
Liang, C., Feng, P., Ku, B., Dotan, I., Canaani, D., Oh, B. H., and Jung, J. U. (2006). Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG, Nat. Cell. Biol., 8(7), 688–699.CrossRefGoogle ScholarPubMed
Lin, S. F., Robinson, D. R., Miller, G., and Kung, H. J. (1999). Kaposi's sarcoma-associated herpesvirus encodes a bZIP protein with homology to BZLF1 of Epstein–Barr virus. J. Virol., 73(3), 1909–1917.Google ScholarPubMed
Lin, R., Genin, P., Mamane, Y.et al. (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.CrossRefGoogle ScholarPubMed
Liu, L., Eby, M. T., Rathore, N., Sinha, S. K., Kumar, A., and Chaudhary, P. M. (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.CrossRefGoogle ScholarPubMed
Low, W., Harries, M., Ye, H., Du, M. Q., Boshoff, C., and Collins, M. (2001). Internal ribosome entry site regulates translation of Kaposi's sarcoma-associated herpesvirus FLICE inhibitory protein. J. Virol., 75(6), 2938–2945.CrossRefGoogle ScholarPubMed
Lubyova, B., Kellum, M. J., Frisancho, A. J., and Pitha, P. M. (2004). Kaposi's sarcoma-associated herpesvirus-encoded vIRF-3 stimulates the transcriptional activity of cellular IRF-3 and IRF-7, J. Biol. Chem., 279(9), pp. 7643–7654.CrossRefGoogle ScholarPubMed
Mann, D. J., Child, E. S., Swanton, C., Laman, H., and Jones, N. (1999). Modulation of p27(Kip1) levels by the cyclin encoded by Kaposi's sarcoma-associated herpesvirus. EMBO J., 18(3), 654–663.CrossRefGoogle ScholarPubMed
Martin, D. F., Kuppermann, B. D., Wolitz, R. A., Palestine, A. G., Li, H., and Robinson, C. A. (1999). Oral ganciclovir for patients with cytomegalovirus retinitis treated with a ganciclovir implant. N. Engl. J. Med., 340(14), 1063–1070.CrossRefGoogle ScholarPubMed
Masood, R., Cesarman, E., Smith, D. L., Gill, P. S., and Flore, O. (2002). Human herpesvirus-8-transformed endothelial cells have functionally activated vascular endothelial growth factor/vascular endothelial growth factor receptor. Am. J. Pathol., 160(1), 23–29.CrossRefGoogle ScholarPubMed
Matta, H. and Chaudhary, P. M. (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. USA, 101(25), 9399–9404.CrossRefGoogle Scholar
Meinl, E., Fickenscher, H., Thome, M., Tschopp, J., and Fleckenstein, B. (1998). Anti-apoptotic strategies of lymphotropic viruses. Immunol. Today, 19(10), 474–479.CrossRefGoogle ScholarPubMed
Mittnacht, S. and Boshoff, C. (2000). Viral cyclins. Rev. Med. Virol., 10(3), 175–184.3.0.CO;2-F>CrossRefGoogle ScholarPubMed
Molden, J., Chang, Y., You, Y., Moore, P. S., and Goldsmith, M. A. (1997). A Kaposi's sarcoma-associated herpesvirus-encoded cytokine homolog (vIL-6) activates signaling through the shared gp130 receptor subunit, J. Biol. Chem., 272(31), 19625–19631.CrossRefGoogle ScholarPubMed
Montaner, S., Sodhi, A., Pece, S., Mesri, E. A., and Gutkind, J. S. (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.Google ScholarPubMed
Montaner, S., Sodhi, A., Molinolo, A.et al. (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(1), 23–36.CrossRefGoogle Scholar
Moore, P. S. (2003). Transplanting cancer: donor-cell transmission of Kaposi sarcoma. Nat. Med., 9(5), 506–508.CrossRefGoogle ScholarPubMed
Moore, P. S. and Chang, Y. (1998). Antiviral activity of tumor-suppressor pathways: clues from molecular piracy by KSHV. Trends Genet., 14(4), 144–150.CrossRefGoogle ScholarPubMed
Moore, P. S. and Chang, Y. (2001). Molecular virology of Kaposi's sarcoma-associated herpesvirus. Phil. Trans. R. Soc. Lond. B Biol. Sci., 356(1408), 499–516.CrossRefGoogle ScholarPubMed
Moore, P. S. and Chang, Y. (2003). Kaposi's sarcoma-associated herpesvirus immunoevasion and tumorigenesis: two sides of the same coin?Annu. Rev. Microbiol., 57, 609–639.CrossRefGoogle ScholarPubMed
Moore, P. S., Boshoff, C., Weiss, R. A., and Chang, Y. (1996). Molecular mimicry of human cytokine and cytokine response pathway genes by KSHV. Science, 274(5293), 1739–1744.CrossRefGoogle ScholarPubMed
Mullberg, J., Geib, T., Jostock, T.et al. (2000). IL-6 receptor independent stimulation of human gp130 by viral IL-6. J. Immunol., 164(9), 4672–4677.CrossRefGoogle ScholarPubMed
Murray, A. W. (2004). Recycling the cell cycle: cyclins revisited, Cell, 116(2), 221–234.CrossRefGoogle ScholarPubMed
Nakamura, H., Li, M., Zarycki, J., and Jung, J. U. (2001). Inhibition of p53 tumor suppressor by viral interferon regulatory factor. J. Virol., 75(16), 7572–7582.CrossRefGoogle ScholarPubMed
Nicholas, J., Ruvolo, V. R., Burns, W. H.et al. (1997). Kaposi's sarcoma-associated human herpesvirus-8 encodes homologues of macrophage inflammatory protein-1 and interleukin-6. Nat. Med., 3(3), 287–292.CrossRefGoogle ScholarPubMed
Oda, E., Ohki, R., Murasawa, H. (2000). Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science, 288(5468), 1053–1058.CrossRefGoogle ScholarPubMed
Ojala, P. M., Yamamoto, K., Castanos-Velez, E., Biberfeld, P., Korsmeyer, S. J., and Makela, T. P. (2000). The apoptotic v-cyclin-CDK6 complex phosphorylates and inactivates Bcl-2. Nat. Cell. Biol., 2(11), 819–825.CrossRefGoogle ScholarPubMed
Osborne, J., Moore, P. S., and Chang, Y. (1999). KSHV-encoded viral IL-6 activates multiple human IL-6 signaling pathways. Hum. Immunol., 60(10), 921–927.CrossRefGoogle ScholarPubMed
Park, J., Seo, T., Hwang, S., Lee, D., Gwack, Y., and Choe, J. (2000). The K-bZIP protein from Kaposi's sarcoma-associated herpesvirus interacts with p53 and represses its transcriptional activity. J. Virol., 74(24), 11977–11982.CrossRefGoogle ScholarPubMed
Parravicini, C., Corbellino, M.Paulli, M.et al. (1997). Expression of a virus-derived cytokine, KSHV vIL-6, in HIV-seronegative Castleman's disease. Am. J. Pathol., 151(6), 1517–1522.Google ScholarPubMed
Parravicini, C., Chandran, B., Corbellino, M.et al. (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.CrossRefGoogle ScholarPubMed
Polson, A. G., Huang, L., Lukac, D. M.et al. (2001). Kaposi's sarcoma-associated herpesvirus K-bZIP protein is phosphorylated by cyclin-dependent kinases. J. Virol., 75(7), 3175–3140.CrossRefGoogle ScholarPubMed
Polson, A. G., Wang, D., DeRisi, J., and Ganem, D. (2002). Modulation of host gene expression by the constitutively active G protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus. Cancer Res., 62(15), 4525–4530.Google ScholarPubMed
Radkov, S. A., Kellam, P., and 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.CrossRefGoogle ScholarPubMed
Rivas, C., Thlick, A. E., Parravicini, C., Moore, P. S., and Chang, Y. (2001). Kaposi's sarcoma-associated herpesvirus LANA2 is a B-cell-specific latent viral protein that inhibits p53. J. Virol., 75(1), 429–438.CrossRefGoogle ScholarPubMed
Russell, I. A., Royds, J. A., and Braithwaite, A. W. (2004). Exploitation of cell cycle and cell death controls by adenoviruses: the road to a productive infection. Prog. Mol. Subcell Biol., 36, 207–243.CrossRefGoogle ScholarPubMed
Russo, J. J., Bohenzky, R. A., Chien, M. C.et al. (1996). Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc. Natl Acad. Sci. USA, 93(25), 14862–14867.CrossRefGoogle Scholar
Sangfelt, O., Erickson, S., Einhorn, S., and Grander, D. (1997). Induction of Cip/Kip and Ink4 cyclin dependent kinase inhibitors by interferon-alpha in hematopoietic cell lines. Oncogene, 14(4), 415–423.CrossRefGoogle ScholarPubMed
Sarid, R., Sato, T., Bohenzky, R. A., Russo, J. J., and Chang, Y. (1997). Kaposi's sarcoma-associated herpesvirus encodes a functional bcl-2 homologue. Nat. Med., 3(3), 293–298.CrossRefGoogle ScholarPubMed
Sarid, R., Wiezorek, J. S., Moore, P. S., and Chang, Y. (1999). Characterization and cell cycle regulation of the major Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) latent genes and their promoter. J. Virol., 73(2), 1438–1446.Google ScholarPubMed
Schuler, M. and Green, D. R. (2001). Mechanisms of p53-dependent apoptosis. Biochem. Soc. Trans., 29(6), 684–688.CrossRefGoogle ScholarPubMed
Seaman, W. T., Ye, D., Wang, R. X., Hale, E. E., Weisse, M., and Quinlivan, E. B. (1999). Gene expression from the ORF50/K8 region of Kaposi's sarcoma-associated herpesvirus. Virology, 263(2), 436–449.CrossRefGoogle ScholarPubMed
Schmid, D., Dengjel, J., Schoor, O., Stevanovic, S., and Munz, C. (2006). Autophagy in innate and adaptive immunity against intracellular pathogens, J. Mol. Med., 84(3), 194–202.CrossRefGoogle ScholarPubMed
Seo, T., Park, J., Lim, C., and Choe, J. (2004). Inhibition of nuclear factor kappa B activity by viral interferon regulatory factor 3 of Kaposi's sarcoma-associated herpesvirus, Oncogene, 23(36), pp. 6146–6155.CrossRefGoogle ScholarPubMed
Sheard, M. A., Uldrijan, S., and Vojtesek, B. (2003). Role of p53 in regulating constitutive and X-radiation-inducible CD95 expression and function in carcinoma cells. Cancer Res., 63(21), 7176–7184.Google ScholarPubMed
Sherr, C. J. (1998). Tumor surveillance via the ARF-p53 pathway. Genes Dev., 12(19), 2984–2991.CrossRefGoogle ScholarPubMed
Sherr, C. J., (2004). Principles of tumor suppression. Cell, 116(2), 235–246.CrossRefGoogle ScholarPubMed
Shin, Y. C., Nakamura, H., Liang, X., Feng, P., Chang, H., Kowalik, T. F., and Jung, J. U. (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.CrossRefGoogle ScholarPubMed
Stine, J. T., Wood, C., Hill, M.et al. (2000). KSHV-encoded CC chemokine vMIP-III is a CCR4 agonist, stimulates angiogenesis, and selectively chemoattracts TH2 cells. Blood, 95(4), 1151–1157.Google ScholarPubMed
Sun, R., Lin, S. F., Staskus, K.et al. (1999). Kinetics of Kaposi's sarcoma-associated herpesvirus gene expression. J. Virol., 73(3), 2232–2242.Google ScholarPubMed
Swanton, C., Mann, D. J., Fleckenstein, B., Neipel, F., Peters, G., and Jones, N. (1997). Herpes viral cyclin/Cdk6 complexes evade inhibition by CDK inhibitor proteins. Nature, 390(6656), 184–187.CrossRefGoogle ScholarPubMed
Swanton, C., Card, G. L., Mann, D., McDonald, N., and Jones, N. (1999). Overcoming inhibitions: subversion of CKI function by viral cyclins. Trends Biochem. Sci., 24(3), 116–120.CrossRefGoogle ScholarPubMed
Takaoka, A., Hayakawa, S., Yanai, H.et al. (2003). Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature, 424(6948), 516–523.CrossRefGoogle ScholarPubMed
Teodoro, J. G. and Branton, P. E. (1997). Regulation of apoptosis by viral gene products. J. Virol., 71, 1739–1746.Google ScholarPubMed
Tomescu, C., Law, W. K., and Kedes, D. H. (2003). Surface downregulation of major histocompatibility complex class I, PE-CAM, and ICAM-1 following de novo infection of endothelial cells with Kaposi's sarcoma-associated herpesvirus. J. Virol., 77(17), 9669–9684.CrossRefGoogle Scholar
Tomita, M., Choe, J., Tsukazaki, T., and Mori, N. (2004). The Kaposi's Sarcoma-associated herpesvirus K-bZIP protein represses transforming growth factor beta signaling through interaction with CREB-binding protein. Oncogene, 23, 8272-8281.CrossRefGoogle ScholarPubMed
Tomlinson, C. C. and Damania, B. (2004). The K1 protein of Kaposi's sarcoma-associated herpesvirus activates the Akt signaling pathway. J. Virol., 78(4), 1918–1927.CrossRefGoogle ScholarPubMed
Urashima, M., Ogata, A., Chauhan, D.et al. (1996). Interleukin-6 promotes multiple myeloma cell growth via phosphorylation of retinoblastoma protein. Blood, 88(6), 2219–2227.Google ScholarPubMed
Urashima, M., Teoh, G., Chauhan, D.et al. (1997). Interleukin-6 overcomes p21WAF1 upregulation and G1 growth arrest induced by dexamethasone and interferon-gamma in multiple myeloma cells. Blood, 90(1), 279–289.Google ScholarPubMed
Dross, R., Yao, S., Asad, S., Westlake, G., Mays, D. J., Barquero, L., Duell, S., Pietenpol, J. A., and Browning, P. J. (2005). Constitutively active K-cyclin/cdk6 kinase in Kaposi sarcoma-associated herpesvirus-infected cells, J. Natl. Cancer Inst., 97(9), 656–666.CrossRefGoogle ScholarPubMed
Verma, S. C., Borah, S., and Robertson, E. S. (2004). Latency-associated nuclear antigen of kaposi's sarcoma-associated herpesvirus up-regulates transcription of human telomerase reverse transcriptase promoter through interaction with transcription factor Sp1. J. Virol., 78(19), 10348–10359.CrossRefGoogle ScholarPubMed
Verschuren, E. W., Hodgson, J. G., Gray, J. W., Kogan, S., Jones, N., and Evan, G. I. (2004a). The role of p53 in suppression of KSHV cyclin-induced lymphomagenesis. Cancer Res., 64(2), 581–589.CrossRefGoogle Scholar
Verschuren, E. W., Jones, N., and Evan, G. I. (2004b). The cell cycle and how it is steered by Kaposi's sarcoma-associated herpesvirus cyclin. J. Gen. Virol., 85(6), 1347–1361.CrossRefGoogle Scholar
Verschuren, E. W., Klefstrom, J., Evan, G. I., and Jones, N. (2002). The oncogenic potential of Kaposi's sarcoma-associated herpesvirus cyclin is exposed by p53 loss in vitro and in vivo. Cancer Cell, 2(3), 229–241.CrossRefGoogle ScholarPubMed
Wang, L., Dittmer, D. P., Tomlinson, C. C., Fakhari, F. D., and Damania, B. (2006). Immortalization of primary endothelial cells by the K1 protein of Kaposi's sarcoma-associated herpesvirus, Cancer Res., 66(7), 3658–3666.CrossRefGoogle ScholarPubMed
Wang, H. W., Sharp, T. V., Koumi, A., Koentges, G., and 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.CrossRefGoogle ScholarPubMed
Wang, L., Wakisaka, N., Tomlinson, C. C.et al. (2004). The Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) K1 protein induces expression of angiogenic and invasion factors. Cancer Res., 64(8), 2774–2781.CrossRefGoogle ScholarPubMed
Wang, S. E., Wu, F. Y., Fujimuro, M., Zong, J., Hayward, S. D., and Hayward, G. S. (2003a). Role of CCAAT/enhancer-binding protein alpha (C/EBPalpha) in activation of the Kaposi's sarcoma-associated herpesvirus (KSHV) lytic-cycle replication-associated protein (RAP) promoter in cooperation with the KSHV replication and transcription activator (RTA) and RAP, J. Virol., 77(1), 600–623.CrossRefGoogle Scholar
Wang, S. E., Wu, F. Y., Yu, Y., and Hayward, G. S. (2003b). CCAAT/enhancer-binding protein-alpha is induced during the early stages of Kaposi's sarcoma-associated herpesvirus (KSHV) lytic cycle reactivation and together with the KSHV replication and transcription activator (RTA) cooperatively stimulates the viral RTA, MTA, and PAN promoters, J. Virol., 77(17), 9590–9612.CrossRefGoogle Scholar
Weitzman, M. D., Carson, C. T., Schwartz, R. A., and Lilley, C. E. (2004). Interactions of viruses with the cellular DNA repair machinery, DNARepair (Amst), 3(8–9), 1165–1173.CrossRefGoogle ScholarPubMed
Widmer, I., Wernli, M., Bachmann, F., Gudat, F., Cathomas, G., and Erb, P. (2002). Differential expression of viral Bcl-2 encoded by Kaposi's sarcoma-associated herpesvirus and human Bcl-2 in primary effusion lymphoma cells and Kaposi's sarcoma lesions. J. Virol., 76(5), 2551–2556.CrossRefGoogle ScholarPubMed
Wood, R. D., Mitchell, M., Sgouros, J., and Lindahl, T. (2001). Human DNA repair genes. Science, 291(5507), 1284–1289.CrossRefGoogle ScholarPubMed
Wu, K. J., Grandori, C., Amacker, M.et al. (1999). Direct activation of TERT transcription by c-MYC. Nat. Genet., 21(2), 220–224.CrossRefGoogle ScholarPubMed
Wu, F. Y., Wang, S. E., Tang, Q. Q.et al. (2003). Cell cycle arrest by Kaposi's sarcoma-associated herpesvirus replication-associated protein is mediated at both the transcriptional and posttranslational levels by binding to CCAAT/enhancer-binding protein alpha and p21(CIP-1). J. Virol., 77(16), 8893–8914.CrossRefGoogle Scholar
Yang, B. T., Chen, S. C., Leach, M. W.et al. (2000). Transgenic expression of the chemokine receptor encoded by human herpesvirus 8 induces an angioproliferative disease resembling Kaposi's sarcoma. J. Exp. Med., 191(3), 445–454.CrossRefGoogle ScholarPubMed
Yu, J., Zhang, L., Hwang, P. M., Kinzler, K. W., and Vogelstein, B. (2001). PUMA induces the rapid apoptosis of colorectal cancer cells. Mol. Cell, 7(3), 673–682.CrossRefGoogle ScholarPubMed
Zhu, Y. M., Bradbury, D. A., Keith, F. J., and Russell, N. (1994). Absence of retinoblastoma protein expression results in autocrine production of interleukin-6 and promotes the autonomous growth of acute myeloid leukemia blast cells. Leukemia, 8(11), 1982–1988.Google ScholarPubMed
Zimring, J. C., Goodbourn, S., and Offermann, M. K. (1998). Human herpesvirus 8 encodes an interferon regulatory factor (IRF) homolog that represses IRF-1-mediated transcription. J. Virol., 72(1), 701–707.Google ScholarPubMed
Zindy, F., Eischen, C. M., Randle, D. H.et al. (1998). Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization. Genes Dev., 12(15), 2424–2433.CrossRefGoogle ScholarPubMed

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