Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 5/16/2006
Publication Date: 5/16/2006
Citation: Cheng, H.H., Kim, T.J., Niikura, M., Hunt, H.D. 2006. Using recombinant viruses to query the functional significance of the protein-protein interactions between chicken MHC class II and Marek's disease virus LORF4 and R-LORF10 [abstract]. International Symposium on Animal Functional Genomics. p. 8.
Technical Abstract: Marek's disease virus (MDV), an alphaherpesvirus, is the causative agent of Marek's disease (MD), the most serious chronic infectious disease problem facing the poultry industry. Being ubiquitous, all birds are exposed to MDV at hatch and susceptible chickens develop T cell lymphomas that result in condemnation (broilers) or reduced production (egg layers). MD vaccines reduce tumor incidence but do not prevent viral replication or spread, which may be the reason for the continued emergence of more virulent MDV strains. To break the cycle of more virulent strains and to augment vaccinal control, poultry breeders are selecting for genetic resistance to MD. To assist this goal, we are using an integrated genomics strategy to identify genes and pathways that confer MD resistance. In one approach that uses a 2-hybrid screen followed by in vitro binding, specific MDV-chicken protein-protein interactions including those between MDV LORF4 and R-LORF10 and MHC class II beta chain and Ii, respectively, were identified. Examination of MHC class II cell surface expression lead to the surprisingly discovery that MDV up-regulates MHC class II both in vitro and in vivo, unlike all other viruses. The up-regulation did not result from interferon or other cytokines as MHC class II expression was confined to infected cells. As MDV is a strictly cell-associated virus and requires activated T cells for its life cycle, this up-regulation of MHC class II in infected cells may contribute to virus spread within the infected host by increasing the chance of contact between productively infected cells and susceptible activated T cells. To determine whether this unique up-regulation of MHC class II was the direct result of the protein interactions, we are taking advantage of the fact that it is possible to generate specific recombinant MDVs. Preliminary results on MHC class II expression with viruses that lack LORF4 and/or R-LORF10 will be presented. This study demonstrates the power of virus-host protein interaction screens and the ability to experimentally manipulate the viral genome for host gene function studies in infectious diseases.