Growth hormone interacts with the Marek's disease virus SORF2 protein and is associated with disease resistance in chicken

Marek's disease (MD) is a lymphoproliferative disease of chickens induced b y a herpesvirus, the MD virus (MDV). Because MD is a significant economic p roblem to the poultry industry, there is great interest in enhancing geneti c resistance, which is controlled by multiple genes. The influence of the M HC has been clearly demonstrated, and several relevant quantitative trait l oci have been mapped; however, no single gene influencing MD resistance has been identified. Transcription of SORF2 is perturbed in the MDV recombinan t clone RM1 due to a solo insertion of the reticuloendotheliosis virus long terminal repeat, which may explain the loss of oncogenicity for this strai n. Hypothesizing that SORF2-interacting host proteins are involved in MD re sistance, we screened a chicken splenic cDNA library by the yeast two-hybri d assay using SORF2 as bait. The chicken growth hormone (GH) structural pep tide was identified, and the specific interaction was verified by coimmunop recipitation. Immunohistochemical staining and indirect immunofluorescence assay indicated that GH and SORF2 can be coexpressed in MDV-infected cells both in vitro and in vivo. Furthermore, polymorphism in the GH gene (GH1) i s associated with the number of tissues with tumors in commercial White Leg horn chickens with the MHC B*2/B*15 genotype. We conclude that GH1 may well be a MD resistance gene.