Skip to main content
SpringerLink
Log in

Marek’s Disease Virus-Induced T-Cell Lymphomas

  • Chapter
  • First Online:
Cancer Associated Viruses

Part of the book series: Current Cancer Research ((CUCR))

Abstract

Marek’s disease (MD) is a prevalent T-cell lymphoma of chickens caused by a cell-associated alphaherpesvirus, Marek’s disease virus (MDV). Since the discovery of the etiological agent in the late 1960s, field strains of MDV have evolved in terms of the level and severity of lesions and the rapidity of lymphoma formation. Consequently, MDV has become an attractive model for the study of lymphomagenesis in a natural host system. Lymphomagenesis by MDV requires the expression of Meq (Marek’s EcoRI-Q-encoded protein), a basic leucine zipper (bZIP) protein expressed during lytic infection, latency, in MDV-induced lymphomas, and derived cell lines. Meq is expressed in both unspliced and spliced forms, and Meq products possess many of the functions associated with viral oncoproteins including the suppression of apoptosis, the induction of proliferation, and the physical association with cell cycle and gene regulatory factors (e.g., p53, Rb, CDK, CtBP-1, HSP-70, etc.). As a bZIP protein, Meq forms homodimers as well as heterodimes with cellular bZIP proteins, most prominently, c-Jun. Both homo- and heterodimerization appear to be crucial to MDV oncogenesis, as is the interaction with the transcriptional repressor CtBP-1. Other MDV-encoded genes contribute to lymphoma progression, including a viral telomerase RNA (vTR), a ubiquitin-specific protease (USP) domain of the major tegument protein (MTP, UL36 gene product), an interleukin 8 homolog (vIL8), RLORF4, a repeat-encoded, short open reading frame of unknown function, and phosphoprotein 14 (pp14). In addition to these genes, several clusters of microRNAs (miRNAs) have been identified that appear to be important to MDV replication and oncogenesis. MDV-mediated lymphomagenesis is associated with the induction of a T-regulatory (Treg) immunophenotype during transformation. The manipulation of the immune response by these transformed Treg cells is believed to contribute to the immunosuppression associated with MD, as well as the progression of MDV-induced lymphomas.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abdul-Careem MF, Hunter BD, Sarson AJ, Mayameei A, Zhou H, Sharif S (2006) Marek’s disease virus-induced transient paralysis is associated with cytokine gene expression in the nervous system. Viral Immunol 19(2):167–176

    Article  PubMed  CAS  Google Scholar 

  • Ajithdoss DK, Reddy SM, Suchodolski PF, Lee LF, Kung HJ, Lupiani B (2009) In vitro characterization of the Meq proteins of Marek’s disease virus vaccine strain CVI988. Virus Res 142(1–2):57–67

    Article  PubMed  CAS  Google Scholar 

  • Anobile JM, Arumugaswami V, Downs D, Czymmek K, Parcells M, Schmidt CJ (2006) Nuclear localization and dynamic properties of the Marek’s disease virus oncogene products Meq and Meq/vIL8. J Virol 80(3):1160–1166

    Article  PubMed  CAS  Google Scholar 

  • Baigent SJ, Davison F (2004) Marek’s Disease Virus: Biology and Life Cycle. In: Davison F, Nair V (eds) Marek’s disease, an evolving problem, vol 1. Elsevier Academic Press, Compton, UK, pp 62–76

    Google Scholar 

  • Biggs PM, Purchase HG, Bee BR, Dalton PJ (1966) Preliminary report on acute Marek’s disease (fowl paralysis) in Great Britain. J Natl Cancer Inst 37(2):199–209

    PubMed  Google Scholar 

  • Bodnar AG, Kim NW, Effros RB, Chiu CP (1996) Mechanism of telomerase induction during T cell activation. Exp Cell Res 228(1):58–64

    Article  PubMed  CAS  Google Scholar 

  • Bradley G, Hayashi M, Lancz G, Tanaka A, Nonoyama M (1989a) Structure of the Marek’s disease virus BamHI-H gene family: genes of putative importance for tumor induction. J Virol 63(6):2534–2542

    PubMed  CAS  Google Scholar 

  • Bradley G, Lancz G, Tanaka A, Nonoyama M (1989b) Loss of Marek’s disease virus tumorigenicity is associated with truncation of RNAs transcribed within BamHI-H. J Virol 63(10):4129–4135

    PubMed  CAS  Google Scholar 

  • Brown AC, Baigent SJ, Smith LP, Chattoo JP, Petherbridge LJ, Hawes P, Allday MJ, Nair V (2006) Interaction of MEQ protein and C-terminal-binding protein is critical for induction of lymphomas by Marek’s disease virus. Proc Natl Acad Sci USA 103(6):1687–1692

    Article  PubMed  CAS  Google Scholar 

  • Brown AC, Smith LP, Kgosana L, Baigent SJ, Nair V, Allday MJ (2009) Homodimerization of the Meq viral oncoprotein is necessary for induction of T-cell lymphoma by Marek’s disease virus. J Virol 83(21):11142–11151

    Article  PubMed  CAS  Google Scholar 

  • Bruton RK, Pelka P, Mapp KL, Fonseca GJ, Torchia J, Turnell AS, Mymryk JS, Grand RJ (2008) Identification of a second CtBP binding site in adenovirus type 5 E1A conserved region 3. J Virol 82(17):8476–8486

    Article  PubMed  CAS  Google Scholar 

  • Burgess SC, Young JR, Baaten BJ, Hunt L, Ross LN, Parcells MS, Kumar PM, Tregaskes CA, Lee LF, Davison TF (2004) Marek’s disease is a natural model for lymphomas overexpressing Hodgkin’s disease antigen (CD30). Proc Natl Acad Sci USA 101(38):13879–13884

    Article  PubMed  CAS  Google Scholar 

  • Burnside J, Bernberg E, Anderson A, Lu C, Meyers BC, Green PJ, Jain N, Isaacs G, Morgan RW (2006) Marek’s disease virus encodes MicroRNAs that map to meq and the latency-associated transcript. J Virol 80(17):8778–8786

    Article  PubMed  CAS  Google Scholar 

  • Buscaglia C, Calnek BW (1988) Maintenance of Marek’s disease herpesvirus latency in vitro by a factor found in conditioned medium. J Gen Virol 69(Pt 11):2809–2818

    Article  PubMed  Google Scholar 

  • Buscaglia C, Calnek BW, Schat KA (1988) Effect of immunocompetence on the establishment and maintenance of latency with Marek’s disease herpesvirus. J Gen Virol 69(Pt 5):1067–1077

    Article  PubMed  Google Scholar 

  • Buza JJ, Burgess SC (2007) Modeling the proteome of a Marek’s disease transformed cell line: a natural animal model for CD30 overexpressing lymphomas. Proteomics 7(8):1316–1326

    Article  PubMed  CAS  Google Scholar 

  • Buza JJ, Burgess SC (2008) Different signaling pathways expressed by chicken naive CD4(+) T cells, CD4(+) lymphocytes activated with staphylococcal enterotoxin B, and those malignantly transformed by Marek’s disease virus. J Proteome Res 7(6):2380–2387

    Article  PubMed  CAS  Google Scholar 

  • Calnek BW (1986) Marek’s disease – a model for herpesvirus oncology. Crit Rev Microbiol 12(4):293–320

    Article  PubMed  CAS  Google Scholar 

  • Calnek BW (1992) Gordon Memorial Lecture. Chicken neoplasia – a model for cancer research. Br Poult Sci 33(1):3–16

    Article  PubMed  CAS  Google Scholar 

  • Calnek BW, Schat KA, Peckham MC, Fabricant J (1983) Field trials with a bivalent vaccine (HVT and SB-1) against Marek’s disease. Avian Dis 27(3):844–849

    Article  PubMed  CAS  Google Scholar 

  • Cantor S, Bell D, Ganesan S, Kass E, Drapkin R, Grossman S, Wahrer D, Sgroi D, Lane W, Haber D, Livingston D (2001) BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function. Cell 105:149–160

    Article  PubMed  CAS  Google Scholar 

  • Ceppi M, Pereira PM, Dunand-Sauthier I, Barras E, Reith W, Santos MA, Pierre P (2009) MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells. Proc Natl Acad Sci USA 106(8):2735–2740

    Article  PubMed  CAS  Google Scholar 

  • Chang JD, Eidson CS, Dykstra MJ, Kleven SH, Fletcher OJ (1983) Vaccination against Marek’s disease and infectious bursal disease. I. Development of a bivalent live vaccine by co-cultivating turkey herpesvirus and infectious bursal disease vaccine viruses in chicken embryo fibroblast monolayers. Poult Sci 62(12):2326–2335

    Article  PubMed  CAS  Google Scholar 

  • Chang JD, Eidson CS, Kleven SH, Fletcher OJ (1984) Vaccination against Marek’s disease and infectious bursal disease. II. Titration and in vivo efficacy of the coinfection-derived bivalent live vaccine for turkey herpesvirus and infectious bursal disease virus. Poult Sci 63(9):1752–1758

    Article  PubMed  CAS  Google Scholar 

  • Chbab N, Egerer A, Veiga I, Jarosinski KW, Osterrieder N (2010) Viral control of vTR expression is critical for efficient formation and dissemination of lymphoma induced by Marek’s disease virus (MDV). Vet Res 41(5):56

    Article  PubMed  CAS  Google Scholar 

  • Chen S, Whetstine JR, Ghosh S, Hanover JA, Gali RR, Grosu P, Shi Y (2009) The conserved NAD(H)-dependent corepressor CTBP-1 regulates Caenorhabditis elegans life span. Proc Natl Acad Sci USA 106(5):1496–1501

    Article  PubMed  CAS  Google Scholar 

  • Chinnadurai G (2007) Transcriptional regulation by C-terminal binding proteins. Int J Biochem Cell Biol 39(9):1593–1607

    Article  PubMed  CAS  Google Scholar 

  • Chinnadurai G (2009) The transcriptional corepressor CtBP: a foe of multiple tumor suppressors. Cancer Res 69(3):731–734

    Article  PubMed  CAS  Google Scholar 

  • Churchill AE (1968) Herpes-type virus isolated in cell culture from tumors of chickens with Marek’s disease. I. Studies in cell culture. J Natl Cancer Inst 41(4):951–956

    PubMed  CAS  Google Scholar 

  • Churchill AE, Biggs PM (1968) Herpes-type virus isolated in cell culture from tumors of chickens with Marek’s disease. II. Studies in vivo. Poult Sci 47(6):2003–2012

    Article  Google Scholar 

  • Cortes PL, Cardona CJ (2004) Pathogenesis of a Marek’s disease virus mutant lacking vIL-8 in resistant and susceptible chickens. Avian Dis 48(1):50–60

    Article  PubMed  Google Scholar 

  • Costinean S, Zanesi N, Pekarsky Y, Tili E, Volinia S, Heerema N, Croce CM (2006) Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E mu-miR155 transgenic mice. Proc Natl Acad Sci USA 103:7024–7029

    Article  PubMed  CAS  Google Scholar 

  • Cui X, Lee LF, Reed WM, Kung HJ, Reddy SM (2004) Marek’s disease virus-encoded vIL-8 gene is involved in early cytolytic infection but dispensable for establishment of latency. J Virol 78(9):4753–4760

    Article  PubMed  CAS  Google Scholar 

  • Cui X, Lee LF, Hunt HD, Reed WM, Lupiani B, Reddy SM (2005) A Marek’s disease virus vIL-8 deletion mutant has attenuated virulence and confers protection against challenge with a very virulent plus strain. Avian Dis 49(2):199–206

    Article  PubMed  Google Scholar 

  • Davison F, Kaiser P (2004) Immunity to Marek’s disease. In: Davison F, Nair V (eds) Marek’s disease, an evolving problem, vol 1. Elsevier, Compton, UK, pp 126–139

    Google Scholar 

  • Delecluse HJ, Hammerschmidt W (1993) Status of Marek’s disease virus in established lymphoma cell lines: herpesvirus integration is common. J Virol 67(1):82–92

    PubMed  CAS  Google Scholar 

  • Delecluse HJ, Schuller S, Hammerschmidt W (1993) Latent Marek’s disease virus can be activated from its chromosomally integrated state in herpesvirus-transformed lymphoma cells. EMBO J 12(8):3277–3286

    PubMed  CAS  Google Scholar 

  • Djeraba A, Kut E, Rasschaert D, Quere P (2002a) Antiviral and antitumoral effects of recombinant chicken myelomonocytic growth factor in virally induced lymphoma. Int Immunopharmacol 2(11):1557–1566

    Article  PubMed  CAS  Google Scholar 

  • Djeraba A, Musset E, Bernardet N, Le Vern Y, Quere P (2002b) Similar pattern of iNOS expression, NO production and cytokine response in genetic and vaccination-acquired resistance to Marek’s disease. Vet Immunol Immunopathol 85(1–2):63–75

    Article  PubMed  CAS  Google Scholar 

  • Djeraba A, Musset E, Lowenthal JW, Boyle DB, Chausse AM, Peloille M, Quere P (2002c) Protective effect of avian myelomonocytic growth factor in infection with Marek’s disease virus. J Virol 76(3):1062–1070

    Article  PubMed  CAS  Google Scholar 

  • Djeraba A, Musset E, van Rooijen N, Quere P (2002d) Resistance and susceptibility to Marek’s disease: nitric oxide synthase/arginase activity balance. Vet Microbiol 86(3):229–244

    Article  PubMed  CAS  Google Scholar 

  • Eis PS, Tam W, SUn L, Chadburn A, Li Z, Gomez MF, Lund E, Dahlberg JE (2005) Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci USA 102:3627–3632

    Article  PubMed  CAS  Google Scholar 

  • Esquela-Kerscher A, Slack FJ (2006) Oncomirs – microRNAs with a role in cancer. Nat Rev Cancer 6(4):259–269

    Article  PubMed  CAS  Google Scholar 

  • Fabricant CG, Hajjar DP, Minick CR, Fabricant J (1981) Herpesvirus infection enhances cholesterol and cholesteryl ester accumulation in cultured arterial smooth muscle cells. Am J Pathol 105(2):176–184

    PubMed  CAS  Google Scholar 

  • Fornari G, Gramantieri L, Ferraci M, Veronese A, Sabbioni S, Calin GA, Grazi GL, Giovannini C, Croce CM, Bolondi L, Negrini M (2008) miR-221 and miR-222 expression affects the proliferation potential of human prostrate carcinoma cell lines by targeting p27Kip1. Oncogene 27:5651–5661

    Article  PubMed  CAS  Google Scholar 

  • Fragnet L, Blasco MA, Klapper W, Rasschaert D (2003) The RNA subunit of telomerase is encoded by Marek’s disease virus. J Virol 77(10):5985–5996

    Article  PubMed  CAS  Google Scholar 

  • Fragnet L, Kut E, Rasschaert D (2005) Comparative functional study of the viral telomerase RNA based on natural mutations. J Biol Chem 280(25):23502–23515

    Article  PubMed  CAS  Google Scholar 

  • Fujii Y, Ikuta K, Kato S, Mikami T, Naiki M (1988) Difference in glycosphingolipid compositions of avian Marek’s disease lymphoma-derived cell lines and lymphoid leukosis lymphoma-derived cell lines. Nippon Juigaku Zasshi 50(2):471–479

    Article  PubMed  CAS  Google Scholar 

  • Garzon R, Calin GA, Croce CM (2009) MicroRNAs in cancer. Annu Rev Med 60:167–179

    Article  PubMed  CAS  Google Scholar 

  • Gimeno IM, Witter RL, Reed WM (1999) Four distinct neurologic syndromes in Marek’s disease: effect of viral strain and pathotype. Avian Dis 43(4):721–737

    Article  PubMed  CAS  Google Scholar 

  • Gimeno IM, Witter RL, Neumann U (2002) Neuropathotyping: a new system to classify Marek’s disease virus. Avian Dis 46(4):909–918

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Haider SA, Ringen LM (1970) Comparative nerve lipid changes in fowl with Marek’s disease detected by thin-layer chromatography. J Virol 5(2):258–261

    Google Scholar 

  • Hajjar DP (1986) Herpesvirus infection prevents activation of cytoplasmic cholesteryl esterase in arterial smooth muscle cells. J Biol Chem 261(17):7611–7614

    PubMed  CAS  Google Scholar 

  • Heidari M, Zhang HM, Sharif S (2008) Marek’s disease virus induces Th-2 activity during cytolytic infection. Viral Immunol 21(2):203–214

    Article  PubMed  CAS  Google Scholar 

  • Hickabottom M, Parker GA, Freemont P, Crook T, Allday MJ (2002) Two nonconsensus sites in the Epstein-Barr virus oncoprotein EBNA3A cooperate to bind the co-repressor carboxyl-terminal-binding protein (CtBP). J Biol Chem 277(49):47197–47204, Epub 2002 Oct 7

    Article  PubMed  CAS  Google Scholar 

  • Hong Y, Coussens PM (1994) Identification of an immediate-early gene in the Marek’s disease virus long internal repeat region which encodes a unique 14-kilodalton polypeptide. J Virol 68(6):3593–3603

    PubMed  CAS  Google Scholar 

  • Hong Y, Frame M, Coussens PM (1995) A 14-kDa immediate-early phosphoprotein is specifically expressed in cells infected with oncogenic Marek’s disease virus strains and their attenuated derivatives. Virology 206(1):695–700

    Article  PubMed  CAS  Google Scholar 

  • Horie M, Ohashi K, Kodama H, Mikami T (1991) Analysis of Marek’s disease tumor-associated surface antigen on MDCC-MSB1-clo. 18 cells. Int J Cancer 47(2):238–243

    Article  PubMed  CAS  Google Scholar 

  • Ikuta K, Kitamoto N, Saito C, Kato S (1980) Demonstration of heterophile antibody in chicken antiserum against Marek’s disease tumor-derived cell line, MSB-1. Biken J 23(1):57–60

    PubMed  CAS  Google Scholar 

  • Ikuta K, Kitamoto N, Shoji H, Kato S, Naiki M (1981) Expression of Forssman antigen of avian lymphoblastoid cell lines transformed by Marek’s disease virus or avian leukosis virus. J Gen Virol 52(Pt 1):145–151

    Article  PubMed  CAS  Google Scholar 

  • Ikuta K, Ueda S, Kato S, Ono K, Osafune S, Yoshida I, Konobe T, Naito I, Naito M, Hirai K (1984) Isolation of monoclonal antibodies reactive with Marek’s disease tumor-associated surface antigen (MATSA). Biken J 27(4):183–188

    PubMed  CAS  Google Scholar 

  • Jarosinski KW, Schat KA (2007) Multiple alternative splicing to exons II and III of viral interleukin-8 (vIL-8) in the Marek’s disease virus genome: the importance of vIL-8 exon I. Virus Genes 34(1):9–22

    Article  PubMed  CAS  Google Scholar 

  • Jarosinski KW, O’Connell PH, Schat KA (2003) Impact of deletions within the Bam HI-L fragment of attenuated Marek’s disease virus on vIL-8 expression and the newly identified transcript of open reading frame LORF4. Virus Genes 26(3):255–269

    Article  PubMed  CAS  Google Scholar 

  • Jarosinski KW, Njaa BL, O’Connell PH, Schat KA (2005a) Pro-inflammatory responses in chicken spleen and brain tissues after infection with very virulent plus Marek’s disease virus. Viral Immunol 18(1):148–161

    Article  PubMed  CAS  Google Scholar 

  • Jarosinski KW, Osterrieder N, Nair VK, Schat KA (2005b) Attenuation of Marek’s disease virus by deletion of open reading frame RLORF4 but not RLORF5a. J Virol 79(18):11647–11659

    Article  PubMed  CAS  Google Scholar 

  • Jarosinski K, Kattenhorn L, Kaufer B, Ploegh H, Osterrieder N (2007) A herpesvirus ubiquitin-specific protease is critical for efficient T cell lymphoma formation. Proc Natl Acad Sci USA 104(50):20025–20030

    Article  PubMed  CAS  Google Scholar 

  • Jones D, Lee L, Liu JL, Kung HJ, Tillotson JK (1992) Marek disease virus encodes a basic-leucine zipper gene resembling the fos/jun oncogenes that is highly expressed in lymphoblastoid tumors [published erratum appears in Proc Natl Acad Sci USA 1993 Mar 15;90(6):2556]. Proc Natl Acad Sci USA 89(9):4042–4046

    Article  PubMed  CAS  Google Scholar 

  • Jones D, Brunovskis P, Witter R, Kung HJ (1996) Retroviral insertional activation in a herpesvirus: transcriptional activation of US genes by an integrated long terminal repeat in a Marek’s disease virus clone. J Virol 70(4):2460–2467

    PubMed  CAS  Google Scholar 

  • Kaiser P, Underwood G, Davison F (2003) Differential cytokine responses following Marek’s disease virus infection of chickens differing in resistance to Marek’s disease. J Virol 77(1):762–768

    Article  PubMed  CAS  Google Scholar 

  • Katiyar S, Jiao X, Wagner E, Lisanti MP, Pestell RG (2007) Somatic excision demonstrates that c-Jun induces cellular migration and invasion through induction of stem cell factor. Mol Cell Biol 27(4):1356–1369

    Article  PubMed  CAS  Google Scholar 

  • Kim S, Kumar PM, Emara MG, Parcells MS (2010) The Meq Protein of Marek’s Disease Virus (MDV) binds to the chicken SKP-1 protein. University of Delaware, Newark, DE

    Google Scholar 

  • Kitamura N, Motoi Y, Mori A, Tatsumi H, Nemoto S, Miyoshi H, Kitamura F, Miyatake S, Hiroi T, Kaminuma O (2009) Suppressive role of C-terminal binding protein 1 in IL-4 synthesis in human T cells. Biochem Biophys Res Commun 382(2):326–330

    Article  PubMed  CAS  Google Scholar 

  • Komander D, Clague MJ, Urbe S (2009) Breaking the chains: structure and function of the deubiquitinases. Nat Rev Mol Cell Biol 10(8):550–563

    Article  PubMed  CAS  Google Scholar 

  • Kumar PM, Arumugaswami V, Dong H, Farnell Y, Dienglewicz RL, Tavlarides-Hontz P, Parcells MS (2010) Spliced gene products of the Meq oncoprotein of Marek’s disease virus (MDV) are expressed during latency, bind to the MDV genome, are potent transcriptional repressors, and induce cellular proliferation. J Virol, in revision

    Google Scholar 

  • Kung HJ, Xia L, Brunovskis P, Li D, Liu JL, Lee LF (2001) Meq: an MDV-specific bZIP transactivator with transforming properties. Curr Top Microbiol Immunol 255:245–260

    Article  PubMed  CAS  Google Scholar 

  • Kuppuswamy M, Vijayalingam S, Zhao LJ, Zhou Y, Subramanian T, Ryerse J, Chinnadurai G (2008) Role of the PLDLS-binding cleft region of CtBP1 in recruitment of core and auxiliary components of the corepressor complex. Mol Cell Biol 28(1):269–281

    Article  PubMed  CAS  Google Scholar 

  • Lambeth LS, Yao Y, Smith LP, Zhao Y, Nair V (2009) MicroRNAs 221 and 222 target p27Kip1 in Marek’s disease virus-transformed tumour cell line MSB-1. J Gen Virol 90(Pt 5):1164–1171

    Article  PubMed  CAS  Google Scholar 

  • Lee LF, Liu X, Sharma JM, Nazerian K, Bacon LD (1983) A monoclonal antibody reactive with Marek’s disease tumor-associated surface antigen. J Immunol 130(2):1007–1011

    PubMed  CAS  Google Scholar 

  • Lee LF, Liu JL, Cui XP, Kung HJ (2003) Marek’s disease virus latent protein MEQ: delineation of an epitope in the BR1 domain involved in nuclear localization. Virus Genes 27(3):211–218

    Article  PubMed  CAS  Google Scholar 

  • Lee S, Sakakibara S, Maruo S, Zhao B, Calderwood MA, Holthaus AM, Lai CY, Takada K, Kieff E, Johannsen E (2009) Epstein-Barr virus nuclear protein 3C domains necessary for lymphoblastoid cell growth: interaction with RBP-Jkappa regulates TCL1. J Virol 83(23):12368–12377

    Article  PubMed  CAS  Google Scholar 

  • Lee LF, Kreager KS, Arango J, Paraguassu A, Beckman B, Zhang H, Fadly A, Lupiani B, Reddy SM (2010) Comparative evaluation of vaccine efficacy of recombinant Marek’s disease virus vaccine lacking Meq oncogene in commercial chickens. Vaccine 28(5):1294–1299

    Article  PubMed  CAS  Google Scholar 

  • Levy AM, Izumiya Y, Brunovskis P, Xia L, Parcells MS, Reddy SM, Lee L, Chen HW, Kung HJ (2003) Characterization of the chromosomal binding sites and dimerization partners of the viral oncoprotein Meq in Marek’s disease virus-transformed T cells. J Virol 77(23):12841–12851

    Article  PubMed  CAS  Google Scholar 

  • Levy AM, Gilad O, Xia L, Izumiya Y, Choi J, Tsalenko A, Yakhini Z, Witter R, Lee L, Cardona CJ, Kung HJ (2005) Marek’s disease virus Meq transforms chicken cells via the v-Jun transcriptional cascade: a converging transforming pathway for avian oncoviruses. Proc Natl Acad Sci USA 102(41):14831–14836

    Article  PubMed  CAS  Google Scholar 

  • Liu JL, Kung HJ (2000) Marek’s disease herpesvirus transforming protein MEQ: a c-Jun analogue with an alternative life style. Virus Genes 21(1–2):51–64

    Article  PubMed  Google Scholar 

  • Liu JL, Lee LF, Ye Y, Qian Z, Kung HJ (1997) Nucleolar and nuclear localization properties of a herpesvirus bZIP oncoprotein, MEQ. J Virol 71(4):3188–3196

    PubMed  CAS  Google Scholar 

  • Liu JL, Ye Y, Lee LF, Kung HJ (1998) Transforming potential of the herpesvirus oncoprotein MEQ: morphological transformation, serum-independent growth, and inhibition of apoptosis. J Virol 72(1):388–395

    PubMed  CAS  Google Scholar 

  • Liu JL, Lin SF, Xia L, Brunovskis P, Li D, Davidson I, Lee LF, Kung HJ (1999a) MEQ and V-IL8: cellular genes in disguise? Acta Virol 43(2–3):94–101

    PubMed  CAS  Google Scholar 

  • Liu JL, Ye Y, Qian Z, Qian Y, Templeton DJ, Lee LF, Kung HJ (1999b) Functional interactions between herpesvirus oncoprotein MEQ and cell cycle regulator CDK2. J Virol 73(5):4208–4219

    PubMed  CAS  Google Scholar 

  • Liu HC, Kung HJ, Fulton JE, Morgan RW, Cheng HH (2001) Growth hormone interacts with the Marek’s disease virus SORF2 protein and is associated with disease resistance in chicken. Proc Natl Acad Sci USA 98(16):9203–9208, Epub 2001 Jul 24

    Article  PubMed  CAS  Google Scholar 

  • Liu HC, Soderblom EJ, Goshe MB (2006) A mass spectrometry-based proteomic approach to study Marek’s Disease Virus gene expression. J Virol Methods 135(1):66–75

    Article  PubMed  CAS  Google Scholar 

  • Lupiani B, Lee LF, Cui X, Gimeno I, Anderson A, Morgan RW, Silva RF, Witter RL, Kung HJ, Reddy SM (2004) Marek’s disease virus-encoded Meq gene is involved in transformation of lymphocytes but is dispensable for replication. Proc Natl Acad Sci USA 101(32):11815–11820, Epub 2004 Aug 2

    Article  PubMed  CAS  Google Scholar 

  • Marek J (1907) Multiple Nervenentzündung (Polyneuritis) bei Hühnern. Dtsch Tierarztl Wochenschr 15:417–421

    Google Scholar 

  • Matsuda H, Ikuta K, Miyamoto H, Kato S (1977) Antibody-induced redistribution of Marek’s disease tumor-associated surface antigen (MATSA) on lymphoblastoid line (MSB-1) cells derived from Marek’s disease lymphoma. Dtsch Tierarztl Wochenschr 84(3):100–104

    Google Scholar 

  • McColl KA, Calnek BW, Harris WV, Schat KA, Lee LF (1987) Expression of a putative tumor-associated surface antigen on normal versus Marek’s disease virus-transformed lymphocytes. J Natl Cancer Inst 79(5):991–1000

    PubMed  CAS  Google Scholar 

  • Montiel E (1995) Masters. University of Delaware, Newark, DE

    Google Scholar 

  • Morgan R, Anderson A, Bernberg E, Kamboj S, Huang E, Lagasse G, Isaacs G, Parcells M, Meyers BC, Green PJ, Burnside J (2008) Sequence conservation and differential expression of Marek’s disease virus microRNAs. J Virol 82(24):12213–12220

    Article  PubMed  CAS  Google Scholar 

  • Morimura T, Hattori M, Ohashi K, Sugimoto C, Onuma M (1995) Immunomodulation of peripheral T cells in chickens infected with Marek’s disease virus: involvement in immunosuppression. J Gen Virol 76(Pt 12):2979–2985

    Article  PubMed  CAS  Google Scholar 

  • Morimura T, Ohashi K, Kon Y, Hattori M, Sugimoto C, Onuma M (1996) Apoptosis and CD8-down-regulation in the thymus of chickens infected with Marek’s disease virus. Arch Virol 141(11):2243–2249

    Article  PubMed  CAS  Google Scholar 

  • Morimura T, Ohashi K, Kon Y, Hattori M, Sugimoto C, Onuma M (1997) Apoptosis in peripheral CD4+T cells and thymocytes by Marek’s disease virus-infection. Leukemia 11(Suppl 3):206–208

    PubMed  Google Scholar 

  • Murthy KK, Calnek BW (1979) Marek’s disease tumor-associated surface antigen (MATSA) in resistant versus susceptible chickens. Avian Dis 23(4):831–837

    Article  PubMed  CAS  Google Scholar 

  • Okazaki W, Purchase HG, Burmester BR (1970) Protection against Marek’s disease by vaccination with a herpesvirus of turkeys. Monatsh Veterinarmed 25(9):353–363

    Google Scholar 

  • Olmeda-Miro N (1996) Masters. University of Delaware, Newark, DE

    Google Scholar 

  • Olmeda-Miro N, Rosenberger JK, Cloud SS, Pope CR (1996) 68th Northeastern conference on avian diseases. Penn State University, Pennsylvania

    Google Scholar 

  • Omar AR, Schat KA (1997) Characterization of Marek’s disease herpesvirus-specific cytotoxic T lymphocytes in chickens inoculated with a non-oncogenic vaccine strain of MDV. Immunology 90(4):579–585

    Article  PubMed  CAS  Google Scholar 

  • Omar AR, Schat KA, Lee LF, Hunt HD (1998) Cytotoxic T lymphocyte response in chickens immunized with a recombinant fowlpox virus expressing Marek’s disease herpesvirus glycoprotein B. Vet Immunol Immunopathol 62(1):73–82

    Article  PubMed  CAS  Google Scholar 

  • Osterrieder N, Kamil JP, Schumacher D, Tischer BK, Trapp S (2006) Marek’s disease virus: from miasma to model. Nat Rev Microbiol 4(4):283–294

    Article  PubMed  CAS  Google Scholar 

  • Pappenheimer AW, Dunn LC, Seidan SM (1929a) Studies on fowl paralysis (Neurolymphomatosis gallinarum). II. Transmission experiments. J Exp Med 49:87–102

    Article  PubMed  CAS  Google Scholar 

  • Pappenheimer AW, Dunn LC, Cone V (1929b) Studies on fowl paralysis (Neurolymphomatosis gallinarum). I. Clinical features and pathology. J Exp Med 49:63–86

    Article  PubMed  CAS  Google Scholar 

  • Parcells MS, Burgess SC (2008) Immunological aspects of Marek’s disease virus (MDV)-induced Lymphoma Progression. In: Kaiser HE, Nasir A (eds) Selected aspects of cancer progression: metastasis, apoptosis and immune response, vol 11. Springer, The Netherlands, pp 169–191

    Chapter  Google Scholar 

  • Parcells MS, Anderson AS, Cantello JL, Morgan RW (1994) Characterization of Marek’s disease virus insertion and deletion mutants that lack US1 (ICP22 homolog), US10, and/or US2 and neighboring short-component open reading frames. J Virol 68(12):8239–8253

    PubMed  CAS  Google Scholar 

  • Parcells MS, Lin SF, Dienglewicz RL, Majerciak V, Robinson DR, Chen HC, Wu Z, Dubyak GR, Brunovskis P, Hunt HD, Lee LF, Kung HJ (2001) Marek’s disease virus (MDV) encodes an interleukin-8 homolog (vIL-8): characterization of the vIL-8 protein and a vIL-8 deletion mutant MDV. J Virol 75(11):5159–5173

    Article  PubMed  CAS  Google Scholar 

  • Peng Q, Shirazi Y (1996) Characterization of the protein product encoded by a splicing variant of the Marek’s disease virus Eco-Q gene (Meq). Virology 226(1):77–82

    Article  PubMed  CAS  Google Scholar 

  • Peng F, Bradley G, Tanaka A, Lancz G, Nonoyama M (1992) Isolation and characterization of cDNAs from BamHI-H gene family RNAs associated with the tumorigenicity of Marek’s disease virus. J Virol 66(12):7389–7396

    PubMed  CAS  Google Scholar 

  • Peng Q, Zeng M, Bhuiyan ZA, Ubukata E, Tanaka A, Nonoyama M, Shirazi Y (1995) Isolation and characterization of Marek’s disease virus (MDV) cDNAs mapping to the BamHI-I2, BamHI-Q2, and BamHI-L fragments of the MDV genome from lymphoblastoid cells transformed and persistently infected with MDV. Virology 213(2):590–599

    Article  PubMed  CAS  Google Scholar 

  • Qian Z, Brunovskis P, Rauscher F 3rd, Lee L, Kung HJ (1995) Transactivation activity of Meq, a Marek’s disease herpesvirus bZIP protein persistently expressed in latently infected transformed T cells. J Virol 69(7):4037–4044

    PubMed  CAS  Google Scholar 

  • Qian Z, Brunovskis P, Lee L, Vogt PK, Kung HJ (1996) Novel DNA binding specificities of a putative herpesvirus bZIP oncoprotein. J Virol 70(10):7161–7170

    PubMed  CAS  Google Scholar 

  • Rath NC, Parcells MS, Xie H, Santin E (2003) Characterization of a spontaneously transformed chicken mononuclear cell line. Vet Immunol Immunopathol 96(1–2):93–104

    Article  PubMed  CAS  Google Scholar 

  • Reddy SM, Lupiani B, Gimeno IM, Silva RF, Lee LF, Witter RL (2002) Rescue of a pathogenic Marek’s disease virus with overlapping cosmid DNAs: use of a pp 38 mutant to validate the technology for the study of gene function. Proc Natl Acad Sci USA 99(10):7054–7059

    Article  PubMed  CAS  Google Scholar 

  • Reichard JF, Sartor MA, Puga A (2008) BACH is a specific repressor of HMOX1 that is inactivated by arsenite. J Biol Chem 283:22363–22370

    Article  PubMed  CAS  Google Scholar 

  • Reinke AW, Grigoryan G, Keating AE (2010) Identification of bZIP interaction partners of viral proteins HBZ, MEQ, BZLF1, and K-bZIP using coiled-coil arrays. Biochemistry 49(9):1985–1997

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Rosenberger JK, Cloud SS, Olmeda-Miro N (1997) Avian tumor virus symposium, Reno, NV

    Google Scholar 

  • Ross N, Binns MM, Sanderson M, Schat KA (1993) Alterations in DNA sequence and RNA transcription of the Bam HI-H fragment accompany attenuation of oncogenic Marek’s disease herpesvirus. Virus Genes 7(1):33–51

    Article  PubMed  CAS  Google Scholar 

  • Schat KA, Calnek BW, Fabricant J (1982a) Characterisation of two highly oncogenic strains of Marek’s disease virus. Avian Pathol 11(4):593–605

    Article  PubMed  CAS  Google Scholar 

  • Schat KA, Chen CL, Shek WR, Calnek BW (1982b) Surface antigens on Marek’s disease lymphoblastoid tumor cell lines. J Natl Cancer Inst 69(3):715–720

    PubMed  CAS  Google Scholar 

  • Shack LA, Buza JJ, Burgess SC (2008) The neoplastically transformed (CD30hi) Marek’s disease lymphoma cell phenotype most closely resembles T-regulatory cells. Cancer Immunol Immunother 57(8):1253–1262

    Article  PubMed  CAS  Google Scholar 

  • Shamblin CE, Greene N, Arumugaswami V, Dienglewicz RL, Parcells MS (2004) Comparative analysis of Marek’s disease virus (MDV) glycoprotein-, lytic antigen pp 38- and transformation antigen Meq-encoding genes: association of meq mutations with MDVs of high virulence. Vet Microbiol 102(3–4):147–167

    Article  PubMed  CAS  Google Scholar 

  • Shek WR, Calnek BW, Schat KA, Chen CH (1983) Characterization of Marek’s disease virus-infected lymphocytes: discrimination between cytolytically and latently infected cells. J Natl Cancer Inst 70(3):485–491

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Solomon JJ, Witter RL, Nazerian K, Burmester BR (1968) Studies on the etiology of Marek’s disease. I. Propagation of the agent in cell culture. Proc Soc Exp Biol Med 127(1):177–182

    Article  PubMed  Google Scholar 

  • Spatz SJ, Petherbridge L, Zhao Y, Nair V (2007) Comparative full-length sequence analysis of oncogenic and vaccine (Rispens) strains of Marek’s disease virus. J Gen Virol 88(Pt 4):1080–1096

    Article  PubMed  CAS  Google Scholar 

  • Su S, Li Y, Sun A, Zhao P, Ding J, Zhu H, Cui Z (2010) Protective immunity of a meq-deleted Marek’s disease virus against very virulent virus challenge in chickens. Wei Sheng Wu Xue Bao 50(3):380–386

    PubMed  CAS  Google Scholar 

  • Suchodolski PF, Izumiya Y, Lupiani B, Ajithdoss DK, Gilad O, Lee LF, Kung HJ, Reddy SM (2009) Homodimerization of Marek’s disease virus-encoded Meq protein is not sufficient for transformation of lymphocytes in chickens. J Virol 83(2):859–869

    Article  PubMed  CAS  Google Scholar 

  • Suchodolski PF, Izumiya Y, Lupiani B, Ajithdoss DK, Lee LF, Kung HJ, Reddy SM (2010) Both homo and heterodimers of Marek’s disease virus encoded Meq protein contribute to transformation of lymphocytes in chickens. Virology 399(2):312–321

    Article  PubMed  CAS  Google Scholar 

  • Swayne DE, Fletcher OJ, Schierman LW (1988) Marek’s disease virus-induced transient paralysis in chickens: alterations in brain density. Acta Neuropathol (Berl) 76(3):287–291

    Article  CAS  Google Scholar 

  • Swayne DE, Fletcher OJ, Schierman LW (1989) Marek’s disease virus-induced transient paralysis in chickens: demonstration of vasogenic brain oedema by an immunohistochemical method. J Comp Pathol 101(4):451–462

    Article  PubMed  CAS  Google Scholar 

  • Tahiri-Alaoui A, Matsuda D, Xu H, Panagiotis P, Burman L, Lambeth LS, Petherbridge L, James W, Mauro V, Nair V (2009a) The 5′ leader of the mRNA encoding the Marek’s disease virus serotype 1 pp 14 protein contains an intronic internal ribosome entry site with allosteric properties. J Virol 83(24):12769–12778

    Article  PubMed  CAS  Google Scholar 

  • Tahiri-Alaoui A, Smith LP, Baigent S, Kgosana L, Petherbridge LJ, Lambeth LS, James W, Nair V (2009b) Identification of an intercistronic IRES in a Marek’s disease virus immediate early gene. J Virol 83(11):5846–5853

    Article  PubMed  CAS  Google Scholar 

  • Tam W, Hughes SH, Hayward WS, Besmer P (2002) Avian bic, a gene isolated from a common retroviral site in avian leukosis virus-induced lymphomas that encodes a noncoding RNA, cooperates with c-myc in lymphomagenesis and erythroleukemogenesis. J Virol 76:4275–4286

    Article  PubMed  CAS  Google Scholar 

  • Trapp S, Parcells MS, Kamil JP, Schumacher D, Tischer BK, Kumar PM, Nair VK, Osterrieder N (2006) A virus-encoded telomerase RNA promotes malignant T cell lymphomagenesis. J Exp Med 203(5):1307–1317

    Article  PubMed  CAS  Google Scholar 

  • Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 103(7):2257–2261

    Article  PubMed  CAS  Google Scholar 

  • Volpini LM, Calnek BW, Sekellick MJ, Marcus PI (1995) Stages of Marek’s disease virus latency defined by variable sensitivity to interferon modulation of viral antigen expression. Vet Microbiol 47(1–2):99–109

    Article  PubMed  CAS  Google Scholar 

  • Waidner LA, Morgan RW, Anderson AS, Bernberg EL, Kamboj S, Garcia M, Riblet SM, Ouyang M, Isaacs GK, Markis M, Meyers BC, Green PJ, Burnside J (2009) MicroRNAs of Gallid and Meleagrid herpesviruses show generally conserved genomic locations and are virus-specific. Virology 388(1):128–136

    Article  PubMed  CAS  Google Scholar 

  • Weinstock D, Schat KA (1987) Virus specific syngeneic killing of reticuloendotheliosis virus transformed cell line target cells by spleen cells. Prog Clin Biol Res 238:253–263

    PubMed  CAS  Google Scholar 

  • Witter RL (1983) Characteristics of Marek’s disease viruses isolated from vaccinated commercial chicken flocks: association of viral pathotype with lymphoma frequency. Avian Dis 27(1):113–132

    Article  PubMed  CAS  Google Scholar 

  • Witter RL (1997) Increased virulence of Marek’s disease virus field isolates. Avian Dis 41(1):149–163

    Article  PubMed  CAS  Google Scholar 

  • Witter RL, Burgoyne GH, Solomon JJ (1969) Evidence for a herpesvirus as an etiologic agent of Marek’s disease. Avian Dis 13(1):211–214

    Article  Google Scholar 

  • Witter RL, Stephens EA, Sharma JM, Nazerian K (1975) Demonstration of a tumor-associated surface antigen in Marek’s disease. J Immunol 115(1):177–183

    PubMed  CAS  Google Scholar 

  • Witter RL, Sharma JM, Lee LF, Opitz HM, Henry CW (1984) Field trials to test the efficacy of polyvalent Marek’s disease vaccines in broilers. Avian Dis 28(1):44–60

    Article  PubMed  CAS  Google Scholar 

  • Witter RL, Li D, Jones D, Lee LF, Kung HJ (1997) Retroviral insertional mutagenesis of a herpesvirus: a Marek’s disease virus mutant attenuated for oncogenicity but not for immunosuppression or in vivo replication. Avian Dis 41(2):407–421

    Article  PubMed  CAS  Google Scholar 

  • Xie Q, Anderson AS, Morgan RW (1996) Marek’s disease virus (MDV) ICP4, pp 38, and meq genes are involved in the maintenance of transformation of MDCC-MSB1 MDV-transformed lymphoblastoid cells. J Virol 70(2):1125–1131

    PubMed  CAS  Google Scholar 

  • Xu H, Yao Y, Zhao Y, Smith LP, Baigent SJ, Nair V (2008) Analysis of the expression profiles of Marek’s disease virus-encoded microRNAs by real-time quantitative PCR. J Virol Methods 149(2):201–208

    Article  PubMed  CAS  Google Scholar 

  • Yao YX, Zhao YG, Xu HT, Smith LP, Lawrie CH, Sewer A, Zavolan M, Nair V (2007) Marek’s disease virus type 2 (MDV-2)-encoded microRNAs show no sequence conservation with those encoded by MDV-1. J Virol 81(13):7164–7170

    Article  PubMed  CAS  Google Scholar 

  • Yao Y, Zhao Y, Xu H, Smith LP, Lawrie CH, Watson M, Nair V (2008) MicroRNA profile of Marek’s disease virus-transformed T-cell line MSB-1: predominance of virus-encoded microRNAs. J Virol 82(8):4007–4015

    Article  PubMed  CAS  Google Scholar 

  • Yao Y, Zhao Y, Smith LP, Lawrie CH, Saunders NJ, Watson M, Nair VK (2009) Differential expression of miRNAs in Marek’s disease virus-transformed T-lymphoma cell lines. J Gen Virol 90(Pt 7):1551–1559

    Article  PubMed  CAS  Google Scholar 

  • Zhao Y, Kurian D, Xu H, Petherbridge L, Smith LP, Hunt L, Nair V (2009a) Interaction of Marek’s disease virus oncoprotein Meq with heat shock protein 70 in lymphoid tumour cells. J Gen Virol 90(Pt 9):2201–2208

    Article  PubMed  CAS  Google Scholar 

  • Zhao Y, Yao Y, Xu H, Lambeth L, Smith LP, Kgosana L, Wang X, Nair V (2009b) A functional MicroRNA-155 ortholog encoded by the oncogenic Marek’s disease virus. J Virol 83(1):489–492

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Drs. Venugopal Nair, Klaus Osterrieder, and Hsing-Jien Kung for the sharing of unpublished data and critical reading of select sections.

Author information

Authors and Affiliations

  1. Department of Animal and Food Sciences, University of Delaware, Newark, DE, 19716, USA

    Mark S. Parcells, Joan Burnside & Robin W. Morgan

  2. Department of Biological Sciences, University of Delaware, 052 Townsend Hall, 531 South College Avenue, Newark, DE, 19716, USA

    Mark S. Parcells

Authors
  1. Mark S. Parcells
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joan Burnside
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robin W. Morgan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark S. Parcells .

Editor information

Editors and Affiliations

  1. Perelman School of Medicine, University of Pennsylvania, Hamilton Walk 3610, Philadelphia, 19104, Pennsylvania, USA

    Erle S. Robertson

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Parcells, M.S., Burnside, J., Morgan, R.W. (2012). Marek’s Disease Virus-Induced T-Cell Lymphomas. In: Robertson, E. (eds) Cancer Associated Viruses. Current Cancer Research. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0016-5_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-0016-5_13

  • Published:

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-9999-3

  • Online ISBN: 978-1-4614-0016-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation