|Liu, Hsiao Ching|
Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/11/2001
Publication Date: N/A
Interpretive Summary: Marek's disease (MD), a virus-induced cancer-like disease of chickens, is considered a major disease problem to the poultry industry. Vaccination has helped to contain the MD incidence, but with the emergence of more virulent viral strains there is great need to develop alternative control strategies. The objective of this research was to identify chicken genes that may confer genetic resistance. We identified that variation in the growth hormone gene can influence MD progression. The information obtained from this research is of great interest to the poultry industry as DNA markers for growth hormone can be used to select chickens with superior MD resistance. Also this work is relevant to the scientist working on human health as it shows that growth hormone can affect the immune response and viral disease resistance.
Technical Abstract: Marek's disease (MD) is a lymphoproliferative disease of chickens induced by a herpesvirus, the Marek's disease virus (MDV). As it is a significant problem to the poultry industry, there is great interest in enhancing genetic resistance, which is controlled by multiple genes. The influence of the major histocompatibility complex (MHC) has been clearly demonstrated, and several quantitative trait loci (QTL) have been mapped, however, no single gene influencing MD resistance has been identified. The MDV recombinant clone RM1 overexpresses SORF2 RNA due to a solo reticuloendotheliosis virus (REV) LTR insertion, which may explain the loss of oncogenicity for this strain. Hypothesizing that host proteins that interact with SORF2 are involved in disease resistance, we screened a splenic cDNA library by the yeast two-hybrid assay using SORF2 as bait. The chicken growth hormone (GH) structural peptide was identified and the specific interaction verified by co-immunoprecipation. Immunohistochemical staining and indirect immunofluorescence assay (IFA) indicate that GH and SORF2 are expressed and can be colocalized in MD tumors. Furthermore, depending on the MHC genotype, polymorphism in the growth hormone gene (GH1) is associated with the number of tumors in a commercial White Leghorn resource population. We conclude that GH1 is likely to be a Marek's disease resistance gene.