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Increased tumorigenicity of cells carrying recombinant human herpesvirus 8

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Summary

Human herpesvirus 8 (HHV-8) infection is associated with the development of Kaposi’s sarcoma and primary effusion lymphoma. The cloning of the HHV-8 genome into a bacterial artificial chromosome (BAC) allows researchers to mutate and identify the relative importance of HHV-8 genes essential for growth and replication in tissue culture systems. However, in vivo models to study the impact of such mutations are very limited. Consequently, the objective of this study was to determine whether cells carrying the HHV-8 BAC would form tumors when injected into mice, enabling the use of this model to assess the influence of viral gene mutation on tumorigenesis. To do so, 293T and 293T-E1 cells carrying recombinant HHV-8 were injected into SCID mice and tumor growth was analyzed. Our results clearly show that mice injected with 293T-E1 cells had a significantly higher tumor incidence level as well as increased tumor volumes and weights compared to mice injected with 293T control cells. Cells carrying the HHV-8 genome grew faster and more aggressively in SCID mice than control 293T cells, highlighting the oncogenic properties of HHV-8. The model presented could therefore be used for the identification of HHV-8 genes contributing to tumorigenesis in the context of the entire viral genome.

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References

  • FQ An HM Folarin N Compitello J Roth SL Gerson KR McCrae FD Fakhari DP Dittmer R Renne (2006) ArticleTitleLong-term-infected telomerase-immortalized endothelial cells: a model for Kaposi’s sarcoma-associated herpesvirus latency in vitro and in vivo J Virol 80 4833–4846 Occurrence Handle16641275 Occurrence Handle10.1128/JVI.80.10.4833-4846.2006 Occurrence Handle1:CAS:528:DC%2BD28XkslChtLw%3D

    Article  PubMed  CAS  Google Scholar 

  • L Arvanitakis E Geras-Raaka A Varma MC Gershengorn E Cesarman (1997) ArticleTitleHuman herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation Nature 385 347–350 Occurrence Handle9002520 Occurrence Handle10.1038/385347a0 Occurrence Handle1:CAS:528:DyaK2sXotF2qtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • L Arvanitakis EA Mesri RG Nador JW Said AS Asch DM Knowles E Cesarman (1996) ArticleTitleEstablishment 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 Occurrence Handle8839859 Occurrence Handle1:CAS:528:DyaK28XmtFSns7k%3D

    PubMed  CAS  Google Scholar 

  • C Bais B Santomasso O Coso L Arvanitakis EG Raaka JS Gutkind AS Asch E Cesarman MC Gershengorn EA Mesri (1998) ArticleTitleG-protein-coupled receptor of Kaposi’s sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator Nature 391 86–89 Occurrence Handle9422510 Occurrence Handle10.1038/34193 Occurrence Handle1:CAS:528:DyaK1cXktVSmug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • C Boshoff SJ Gao LE Healy S Matthews AJ Thomas L Coignet RA Warnke JA Strauchen E Matutes OW Kamel PS Moore RA Weiss Y Chang (1998) ArticleTitleEstablishing a KSHV + cell line (BCP-1) from peripheral blood and characterizing its growth in Nod/SCID mice Blood 91 1671–1679 Occurrence Handle9473233 Occurrence Handle1:CAS:528:DyaK1cXht12gtr4%3D

    PubMed  CAS  Google Scholar 

  • E Cesarman Y Chang PS Moore JW Said DM Knowles (1995a) ArticleTitleKaposi’s sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas N Engl J Med 332 1186–1191 Occurrence Handle10.1056/NEJM199505043321802 Occurrence Handle1:CAS:528:DyaK2MXlvFCqtr4%3D

    Article  CAS  Google Scholar 

  • E Cesarman PS Moore PH Rao G Inghirami DM Knowles Y Chang (1995b) ArticleTitleIn vitro establishment and characterization of two acquired immunodeficiency syndrome-related lymphoma cell lines (BC-1 and BC-2) containing Kaposi’s sarcoma-associated herpesvirus-like (KSHV) DNA sequences Blood 86 2708–2714 Occurrence Handle1:CAS:528:DyaK2MXot1Ogs7s%3D

    CAS  Google Scholar 

  • Y Chang E Cesarman MS Pessin F Lee J Culpepper DM Knowles PS Moore (1994) ArticleTitleIdentification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma Science 266 1865–1869 Occurrence Handle7997879 Occurrence Handle10.1126/science.7997879 Occurrence Handle1:CAS:528:DyaK2MXislCjs78%3D

    Article  PubMed  CAS  Google Scholar 

  • DM Ciufo JS Cannon LJ Poole FY Wu P Murray RF Ambinder GS Hayward (2001) ArticleTitleSpindle cell conversion by Kaposi’s sarcoma-associated herpesvirus: formation of colonies and plaques with mixed lytic and latent gene expression in infected primary dermal microvascular endothelial cell cultures J Virol 75 5614–5626 Occurrence Handle11356969 Occurrence Handle10.1128/JVI.75.12.5614-5626.2001 Occurrence Handle1:CAS:528:DC%2BD3MXjvFyrsbg%3D

    Article  PubMed  CAS  Google Scholar 

  • M Djerbi V Screpanti AI Catrina B Bogen P Biberfeld A Grandien (1999) ArticleTitleThe inhibitor of death receptor signaling, FLICE-inhibitory protein defines a new class of tumor progression factors J Exp Med 190 1025–1032 Occurrence Handle10510092 Occurrence Handle10.1084/jem.190.7.1025 Occurrence Handle1:CAS:528:DyaK1MXmsVClt7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • O Flore S Rafii S Ely JJ O’Leary EM Hyjek E Cesarman (1998) ArticleTitleTransformation of primary human endothelial cells by Kaposi’s sarcoma-associated herpesvirus Nature 394 588–592 Occurrence Handle9707121 Occurrence Handle10.1038/29093 Occurrence Handle1:CAS:528:DyaK1cXltlykur4%3D

    Article  PubMed  CAS  Google Scholar 

  • SJ Gao C Boshoff S Jayachandra RA Weiss Y Chang PS Moore (1997) ArticleTitleKSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway Oncogene 15 1979–1985 Occurrence Handle9365244 Occurrence Handle10.1038/sj.onc.1201571 Occurrence Handle1:CAS:528:DyaK2sXntFegsbc%3D

    Article  PubMed  CAS  Google Scholar 

  • HH Krishnan PP Naranatt MS Smith L Zeng C Bloomer B Chandran (2004) ArticleTitleConcurrent 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 3601–3620 Occurrence Handle15016882 Occurrence Handle10.1128/JVI.78.7.3601-3620.2004 Occurrence Handle1:CAS:528:DC%2BD2cXis1Klurw%3D

    Article  PubMed  CAS  Google Scholar 

  • HH Krishnan N Sharma-Walia L Zeng SJ Gao B Chandran (2005) ArticleTitleEnvelope glycoprotein B of Kaposi’s sarcoma-associated herpesvirus is essential for egress from infected cells J Virol 79 10952–10967 Occurrence Handle16103147 Occurrence Handle10.1128/JVI.79.17.10952-10967.2005 Occurrence Handle1:CAS:528:DC%2BD2MXps1Gls7k%3D

    Article  PubMed  CAS  Google Scholar 

  • BS Lee M Connole Z Tang NL Harris JU Jung (2003) ArticleTitleStructural analysis of the Kaposi’s sarcoma-associated herpesvirus K1 protein J Virol 77 8072–8086 Occurrence Handle12829846 Occurrence Handle10.1128/JVI.77.14.8072-8086.2003 Occurrence Handle1:CAS:528:DC%2BD3sXlt1Kkurk%3D

    Article  PubMed  CAS  Google Scholar 

  • H Lee R Veazey K Williams M Li J Guo F Neipel B Fleckenstein A Lackner RC Desrosiers JU Jung (1998) ArticleTitleDeregulation of cell growth by the K1 gene of Kaposi’s sarcoma-associated herpesvirus Nat Med 4 435–440 Occurrence Handle9546789 Occurrence Handle10.1038/nm0498-435 Occurrence Handle1:CAS:528:DyaK1cXisVelt7c%3D

    Article  PubMed  CAS  Google Scholar 

  • AD Mutlu LE Cavallin L Vincent C Chiozzini P Eroles EM Duran Z Asgari AT Hooper KM La Perle C Hilsher SJ Gao DP Dittmer S Rafii EA Mesri (2007) ArticleTitleIn vivo-restricted and reversible malignancy induced by human herpesvirus-8 KSHV: a cell and animal model of virally induced Kaposi’s sarcoma Cancer Cell 11 245–258 Occurrence Handle17349582 Occurrence Handle10.1016/j.ccr.2007.01.015 Occurrence Handle1:CAS:528:DC%2BD2sXjsVymtLw%3D

    Article  PubMed  CAS  Google Scholar 

  • CH Parsons LA Adang J Overdevest CM O’Connor JR Taylor D Camerini DH Kedes (2006) ArticleTitleKSHV targets multiple leukocyte lineages during long-term productive infection in NOD/SCID mice J Clin Invest 116 1963–1973 Occurrence Handle16794734 Occurrence Handle10.1172/JCI27249 Occurrence Handle1:CAS:528:DC%2BD28XmvV2lurs%3D

    Article  PubMed  CAS  Google Scholar 

  • GR Picchio RE Sabbe RJ Gulizia M McGrath BG Herndier DE Mosier (1997) ArticleTitleThe KSHV/HHV8-infected BCBL-1 lymphoma line causes tumors in SCID mice but fails to transmit virus to a human peripheral blood mononuclear cell graft Virology 238 22–29 Occurrence Handle9375005 Occurrence Handle10.1006/viro.1997.8822 Occurrence Handle1:CAS:528:DyaK2sXntlOrtLs%3D

    Article  PubMed  CAS  Google Scholar 

  • S Portes-Sentis E Manet G Gourru A Sergeant H Gruffat (2001) ArticleTitleIdentification of a short amino acid sequence essential for efficient nuclear targeting of the Kaposi’s sarcoma-associated herpesvirus/human herpesvirus-8 K8 protein J Gen Virol 82 507–512 Occurrence Handle11172091 Occurrence Handle1:CAS:528:DC%2BD3MXhs1SjsLY%3D

    PubMed  CAS  Google Scholar 

  • O Prakash ZY Tang X Peng R Coleman J Gill G Farr F Samaniego (2002) ArticleTitleTumorigenesis and aberrant signaling in transgenic mice expressing the human herpesvirus-8 K1 gene J Natl Cancer Inst 94 926–935 Occurrence Handle12072546 Occurrence Handle1:CAS:528:DC%2BD38XltlKrsrk%3D

    PubMed  CAS  Google Scholar 

  • R Renne D Dittmer D Kedes K Schmidt RC Desrosiers PA Luciw D Ganem (2004) ArticleTitleExperimental transmission of Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8) to SIV-positive and SIV-negative rhesus macaques J Med Primatol 33 1–9 Occurrence Handle15061726 Occurrence Handle10.1046/j.1600-0684.2003.00043.x Occurrence Handle1:STN:280:DC%2BD2c7mvFyjtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • R Renne W Zhong B Herndier M McGrath N Abbey D Kedes D Ganem (1996) ArticleTitleLytic growth of Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) in culture Nat Med 2 342–346 Occurrence Handle8612236 Occurrence Handle10.1038/nm0396-342 Occurrence Handle1:CAS:528:DyaK28XhsVGkt7c%3D

    Article  PubMed  CAS  Google Scholar 

  • J Soulier L Grollet E Oksenhendler P Cacoub D Cazals-Hatem P Babinet MF d’Agay JP Clauvel M Raphael L Degos et al. (1995) ArticleTitleKaposi’s sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman’s disease Blood 86 1276–1280 Occurrence Handle7632932 Occurrence Handle1:CAS:528:DyaK2MXnsVClsL0%3D

    PubMed  CAS  Google Scholar 

  • MR Staudt Y Kanan JH Jeong JF Papin R Hines-Boykin DP Dittmer (2004) ArticleTitleThe tumor microenvironment controls primary effusion lymphoma growth in vivo Cancer Res 64 4790–4799 Occurrence Handle15256448 Occurrence Handle10.1158/0008-5472.CAN-03-3835 Occurrence Handle1:CAS:528:DC%2BD2cXls1Omsb8%3D

    Article  PubMed  CAS  Google Scholar 

  • W Wu R Rochford L Toomey W Harrington SuffixJr G Feuer (2005) ArticleTitleInhibition of HHV-8/KSHV infected primary effusion lymphomas in NOD/SCID mice by azidothymidine and interferon-alpha Leuk Res 29 545–555 Occurrence Handle15755507 Occurrence Handle10.1016/j.leukres.2004.11.010 Occurrence Handle1:CAS:528:DC%2BD2MXitFCjsrc%3D

    Article  PubMed  CAS  Google Scholar 

  • Y Xu DP AuCoin AR Huete SA Cei LJ Hanson GS Pari (2005) ArticleTitleA Kaposi’s sarcoma-associated herpesvirus/human herpesvirus 8 ORF50 deletion mutant is defective for reactivation of latent virus and DNA replication J Virol 79 3479–3487 Occurrence Handle15731242 Occurrence Handle10.1128/JVI.79.6.3479-3487.2005 Occurrence Handle1:CAS:528:DC%2BD2MXit1ehsrg%3D

    Article  PubMed  CAS  Google Scholar 

  • FC Ye FC Zhou SM Yoo JP Xie PJ Browning SJ Gao (2004) ArticleTitleDisruption of Kaposi’s sarcoma-associated herpesvirus latent nuclear antigen leads to abortive episome persistence J Virol 78 11121–11129 Occurrence Handle15452232 Occurrence Handle10.1128/JVI.78.20.11121-11129.2004 Occurrence Handle1:CAS:528:DC%2BD2cXotlKisro%3D

    Article  PubMed  CAS  Google Scholar 

  • SM Yoo FC Zhou FC Ye HY Pan SJ Gao (2005) ArticleTitleEarly and sustained expression of latent and host modulating genes in coordinated transcriptional program of KSHV productive primary infection of human primary endothelial cells Virology 343 47–64 Occurrence Handle16154170 Occurrence Handle10.1016/j.virol.2005.08.018 Occurrence Handle1:CAS:528:DC%2BD2MXht1Wjur7M

    Article  PubMed  CAS  Google Scholar 

  • FC Zhou YJ Zhang JH Deng XP Wang HY Pan E Hettler SJ Gao (2002) ArticleTitleEfficient infection by a recombinant Kaposi’s sarcoma-associated herpesvirus cloned in a bacterial artificial chromosome: application for genetic analysis J Virol 76 6185–6196 Occurrence Handle12021352 Occurrence Handle10.1128/JVI.76.12.6185-6196.2002 Occurrence Handle1:CAS:528:DC%2BD38XktlSqsLw%3D

    Article  PubMed  CAS  Google Scholar 

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Correspondence to L. Flamand.

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Correspondence: Louis Flamand Ph.D., Rheumatology and Immunology Research Center, CHUL Research Center, Room T1-49, 2705 Laurier blvd, Sainte-Foy, Quebec, Canada G1V 4G2

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Cloutier, N., van Eyll, O., Janelle, ME. et al. Increased tumorigenicity of cells carrying recombinant human herpesvirus 8. Arch Virol 153, 93–103 (2008). https://doi.org/10.1007/s00705-007-1072-4

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  • DOI: https://doi.org/10.1007/s00705-007-1072-4

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