Identification of chicken lymphocyte antigen 6 complex, locus E (<i>LY6E</i>, alias <i>SCA2</i>) as a putative Marek’s disease resistance gene via a virus-host protein interaction screen

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 <i>E. coli</i> 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, <i>LY6E </i>was found to be significantly associated with MD traits in an MD resource population comprised of commercial chickens. Previously, <i>LY6E</i> was implicated in two independent DNA microarray experiments evaluating differential gene expression following MDV infection. Given that <i>LY6E</i> is involved in T cell differentiation and activation, we suggest that <i>LY6E</i> 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.