|Liu, Hsiao Ching|
Submitted to: Cytogenetics and Genome Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/28/2003
Publication Date: 2/17/2004
Citation: Liu, H., Niikura, M., Fulton, J.E., Cheng, H.H. 2003. Identification of chicken lymphocyte antigen 6 complex, locus e (LY6E, alias SCA2) as a putative Marek's disease resistance gene via a virus-host protein interaction screen. Cytogenetics and Genome Research. 102:304-308. (DOI:10.1159/000075767). Interpretive Summary: Marek's disease (MD) is an economically-important disease of chickens caused by a pathogenic virus. Currently, vaccines have controlled the problem but new emerging viral strains that vaccines cannot control are being encountered more frequently. To help combat MD, chickens are being selected for genetic resistance. Biotechnology may greatly enhance the rate of poultry breeding improvement by identifying the genes responsible for conferring resistance. Using a novel integrative strategy that capitalizes on virus-chicken protein interactions, this study identified a chicken gene known as stem cell antigen 2 or SCA2 that is an MD resistance gene. As a result, genetic markers to this gene can be used to generate more disease-resistant chickens. Furthermore, the identification of this gene provides insights on what immune responses help fight the disease. Ultimately, consumers will benefit as losses due to disease are reduced.
Technical Abstract: 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 gene 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 SCA2, also known as TSA1, was found to specifically interact with US10. This interaction was confirmed by an in vitro protein binding assay. Furthermore, SCA2 was found to be significantly associated with MD traits in a MD resource population comprised of commercial chickens. Previously, SCA2 was implicated in two independent DNA microarray experiments evaluating differential gene expression following MDV infection. Given that SCA2 is involved in T cell differentiation and activation, we suggest that SCA2 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.