MAREK'S DISEASE (MD), IS A HIGHLY CONTAGIOUSDISEASE IN POULTRY CAUSED BY MAREK'S DISEASE VIRUS (MDV), AN ALPHAHERPESVIRUS. MD IS A MAJOR ECONOMIC THREAT TO FARMED POULTRY. CURRENTLY, MD IS CONTROLLED BY UNIVERSAL VACCINATION WITH A LIVE ATTENUATED VIRUS STRAIN CALLED "RISPENS, " OR CVI988 STRAIN. ALTHOUGH THIS STRAIN PROVIDES SUFFICIENT PROTECTION AGAINST NEARLY ALL FIELD ISOLATES, RECENT HISTORY TELLS US THAT WITH TIME NEW VIRULENT STRAINS WILL EVOLVE, EMERGE, AND BREAK THE CURRENT PROTECTION. HEREIN WE PROPOSE TO DEVELOP NEW LIVE ATTENUATED VACCINE STRAINS FOR MD. FIRST, WE WILL IDENTIFY HERETOFORE-UNKNOWN VIRULENCE FACTORS WHICH INHIBIT THE PRODUCTION OF THE TYPE I INTERFERONS (IFNS), WHICH ARE PROTEINS THAT REGULATE THE ACTIVITY OF THE IMMUNE SYSTEM. SECOND, WE WILL USE THIS NEW INFORMATION TO RATIONALLY DESIGN RECOMBINANT MUTANTS OF MDV WHICH ARE COMPROMISED FOR THEIR ABILITY TO INHIBIT THE PRODUCTION OF VIRULENCE FACTORS WHICH INHIBIT THE PRODUCTION OF TYPE I IFNS. INFECTION WITH THESE POTENTIAL VACCINE STRAINS WILL RESULT IN THE PRODUCTION OF GREATER AMOUNTS OF TYPE I IFNS, WHICH WILL IN TURN IMPROVE THE IMMUNE RESPONSEAND IMPROVE THEIR VACCINAL PROTECTION. WE HAVE ESTABLISHED A COLLABORATION WITH THE BOEKE LABORATORY (NYULANGONE) WHICH IS EXPERT IN THE ASSEMBLY OF LARGE GENOMES. WE WILL RELY UPON THEM FOR RANDOMLY MUTATED GENES TO IDENTIFY FUNCTIONALLY RELEVANT PORTIONS OF THE VIRUS, AND TO SYNTHESIZE WHOLE MDV VIRUSES FOR TESTING. IF SUCCESSFUL, THIS PROJECT WILL RESULT IN NEW AND MORE PROTECTIVE VACCINE STRAINS FOR MDV, SUITABLE FOR COMMERCIAL USE.