Marek’s disease virus (MDV) is a naturally occurring oncogenic avian herpesvirus that causes neurological disorders and T cell lymphoma disease in domestic chickens. Identification and functional characterization of the individual factors involved in Marek’s disease (MD) resistance or pathogenesis will enhance our understanding of MDV pathogenesis and further genetic improvement of chickens. To study the genetic basis for resistance to MD, a strategy that combined protein-protein interaction screens followed by linkage analysis was performed. The MDV protein US10 was used as the bait in an E. coli two-hybrid screening of a cDNA library derived from activated splenic T cells. The chicken LY6E, also known as SCA2 and TSA1, was found to specifically interact with US10. This interaction was confirmed by an in vitro protein-binding assay. Furthermore, LY6E was found to be significantly associated with MD traits in an MD resource population comprised of commercial chickens. Previously, LY6E was implicated in two independent DNA microarray experiments evaluating differential gene expression following MDV infection. Given that LY6E is involved in T cell differentiation and activation, we suggest that LY6E is a candidate gene for MD resistance and deserves further investigation on its role in MDV pathogenesis, especially with respect to the binding of US10.   

1.
Bacon LD, Hunt HD, Cheng HH: Genetic resistance to Marek’s Disease, in Hirai K (ed): Marek’s Disease, pp 121–142 (Springer, New York 2001).
2.
Brunovskis P, Velicer LF: The Marek’s disease virus (MDV) unique short region: alpha herpesvirus – homologous, fowlpox virus – homologous, and MDV-specific genes. Virology 206:324–338 (1995).
3.
Bumstead N: Genomic mapping of resistance to Marek’s disease. Avian Pathol 27:S78–S81 (1998).
4.
Burgess SC, Basaran BH, Davison TF: Resistance to Marek’s disease herpesvirus-induced lymphoma is multiphasic and dependent on host genotypes. Vet Pathol 38:129–141 (2001).
5.
Buscaglia C, Calnek BW: Maintenance of Marek’s disease herpesvirus latency in vitro by a factor found in conditioned medium. J Gen Virol 69:2809–2818 (1988).
6.
Calnek BW, Schat KA, Ross LJN, Shek WR, Chen C-LH: Further characterization of Marek’s disease virus-infected lymphocytes. I. In vivo infection. Int J Cancer 33:389–398 (1984).
7.
Calnek BW, Witter RL: Marek’s disease, in Calnek BW, Barnes HJ, Beard CW, McDougald LR, Saif YM (eds): Diseases of Poultry, pp 369–413 (Iowa State University Press, Ames 1997).
8.
Cheng HH: Selection for disease resistance: molecular genetic techniques, in Muir WM, Aggrey SE (eds): Poultry Genetics, Breeding and Technology, pp. 385–398 (CABI Publishing, Cambridge, MA 2003).
9.
Churchill AE, Biggs PM: Agent of Marek’s disease in tissue culture. Nature 215:528–530 (1967).
10.
Classon BJ, Coverdale L: Mouse stem cell antigen Sca-2 is a member of the Ly-6 family of cell surface proteins. Proc natl Acad Sci, USA 91:5296–5300 (1994).
11.
Derfuss T, Meinl E: Herpesviral proteins regulating apoptosis. Curr Top Microbiol Immunol 269:257–272 (2002).
12.
Fleming TJ, O’hUigin C, Malek TR: Characterization of two novel Ly-6 genes. Protein sequence and potential structural similarity to alpha-bungarotoxin and other neurotoxins. J Immunol 150:5379–5390 (1993).
13.
Jones D, Brunovskis P, Witter R, Kung H: 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 70:2460–2467 (1996).
14.
Lee LF, Wu P, Sui D, Ren D, Kamil J, Kung HJ, Witter RL: The complete unique long sequence and the overall genomic organization of the GA strain of Marek’s disease virus. Proc natl Acad Sci, USA 97:6091–6096 (2000).
15.
Liu HC, Cheng HH: Genetic mapping of the chicken stem cell antigen 2 (SCA2) gene to chromosome 2 via PCR primer mutagenesis. Anim Genet 34:158–160 (2003).
16.
Liu H-C, Cheng HH, Softer L, Burnside J: A strategy to identify positional candidate genes conferring Marek’s disease resistance by integrating DNA microarrays with genetic mapping. Anim Genet 32:351–359 (2001a).
17.
Liu H-C, Kung H-J, Fulton JE, Morgan RW, Cheng HH: Growth hormone interacts with the Marek’s disease virus SORF2 protein and is associated with disease resistance in chicken. Proc natl Acad Sci, USA 98:9203–9208 (2001b).
18.
MacNeil I., Kennedy J, Godfrey DI, Jenkins NA, Masciantonio M, Mineo C, Gilbert DJ, Copeland NG, Boyd RL, Zlotnik A: Isolation of a cDNA encoding thymic shared antigen-1. A new member of the Ly6 family with a possible role in T cell development. J Immunol 151:6913–6923 (1993).
19.
Morgan RW, Softer L, Anderson AS, Bernberg L, Cui J, Burnside J: Induction of host gene expression following infection of chicken embryo fibroblasts with oncogenic Marek’s disease virus. J Virol 75:533–539 (2001).
20.
Nazerian K, Burmester BR: Electron microscopy of a herpesvirus associated with the agent of Marek’s disease in cell culture. Cancer Res 28:2454–2462 (1968).
21.
Noda S, Kosugi A, Saitoh S-I, Narumiya S, Hamaoka T: Protection from anti-TCR/CD3-induced apoptosis in immature thymocytes by a signal through thymic shared antigen-1/stem cell antigen-2. J exp Med 183:2355–2360 (1996).
22.
Parcells MS, Anderson AS, Cantello JL, Morgan RW: 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 68:8239–8253 (1994).
23.
Petrenko O, Ischenko I, Enrietto PJ: Characterization of changes in gene expression associated with malignant transformation by the NF-κB family member, v-Rel. Oncogene 15:1671–1680 (1997).
24.
Purchase HG: Clinical disease and its economic impact, in Payne LN (ed): Marek’s Disease, Scientific Basis and Methods of Control, pp 17–42 (Martinus Nijhoff Publishing, Boston 1985).
25.
Saitoh S-I, Kosugi A, Noda S, Yamamoto N, Ogata M, Minami Y, Miyake K, Hamaoka T: Modulation of TCR-mediated signaling pathway by thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2). J Immunol 155:5574–5581 (1995).
26.
Schat KA, Chen C-LH, Shek WR, Calnek BW: Surface antigens on Marek’s disease lymphoblastoid tumor cell lines. J natl Cancer Inst 69:715–720 (1982).
27.
Shek WR, Calnek BW, Schat KA, Chen CLH: Characterization of Marek’s disease virus-infected lymphocytes: discrimination between cytolytically and latently infected cells. J natl Canc Inst 70:485–491 (1983).
28.
Tulin EE, Onoda N, Nakata Y, Maeda M, Hasegawa M, Nomura H, Kitamura T: SF20/IL-25, a novel bone marrow stroma-derived growth factor that binds to mouse thymic shared antigen-1 and supports lymphoid cell proliferation. J Immunol 167:6338–6347 (2001).
29.
Tulman ER, Afonso CL, Lu Z, Zsak L, Rock DL, Kutish GF: The genome of a very virulent Marek’s disease virus. J Virol 74:7980–7988 (2000).
30.
Vallejo RL, Bacon LD, Liu H-C, Witter RL, Groenen MAM, Hillel J, Cheng HH: Genetic mapping of quantitative trait loci affecting susceptibility to Marek’s disease virus induced tumors in F2 intercross chickens. Genetics 148:349–360 (1998).
31.
Waanders GA, Godfrey DI, Boyd RL: Modulation of T cell differentiation in murine fetal thymus organ cultures. Thymus 13:73–82 (1989).
32.
Witter RL: Increased virulence of Marek’s disease virus field isolates. Avian Dis 41:149–163 (1997).
33.
Yonash N, Bacon LD, Witter RL, Cheng HH: Higher resolution mapping and identification of quantitative trait loci (QTL) affecting susceptibility to Marek’s disease. Anim Genet 30:126–135 (1999).
34.
Zammit DJ, Berzins SP, Gill JW, Randle-Barrett ES, Barnett L, Koentgen F, Lambert GW, Harvey RP, Boyd RL, Classon BJ: Essential role for the lymphostromal plasma membrane Ly-6 superfamily molecule thymic shared antigen 1 in development of the embryonic adrenal gland. Mol Cell Biol 22:946–952 (2002).
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