title: Addition of a UL5 helicase-primase subunit point mutation eliminates bursal-thymic atrophy of Marek's disease virus ∆Meq recombinant virus but reduces vaccinal protection.
abstract: Marek's disease virus (MDV) is an oncogenic alphaherpesvirus and the causative agent of Marek's disease (MD), characterized by immunosuppression, paralysis, nerve enlargement and induction of T-cell lymphomas in chickens. Despite widespread usage of vaccines since the 1970s to control MD, more virulent field strains of MDV have emerged that overcome vaccinal protection, necessitating the development of new and more protective MD vaccines. The ∆Meq virus, a recombinant Md5 strain MDV lacking the viral oncogene Meq, is one candidate MD vaccine with great potential but unfortunately it also causes bursal-thymic atrophy (BTA) in maternal antibody negative chickens, raising concerns that impede commercial use as a vaccine. Previously, we identified a point mutation within UL5 that reduced in vivo replication in attenuated viruses. We proposed that introduction of the UL5 point mutation into the ∆Meq virus would reduce in vivo replication and eliminate BTA yet potentially retain high protective abilities. In birds, the ∆Meq+UL5 recombinant MDV had reduced replication compared to the original ∆Meq virus, while weights of lymphoid organs indicated that ∆Meq+UL5 did not induce BTA, supporting the hypothesis that reduction of in vivo replication would also abolish BTA. Vaccine trials of the ∆Meq+UL5 virus compared to other ∆Meq-based viruses and commercial vaccines show that, while the ∆Meq+UL5 does provide vaccinal protection, this protection was also reduced compared to the original ∆Meq virus. Therefore, it appears that a very delicate balance is required between levels of replication able to induce high vaccinal protection, yet not so high as to induce BTA.
authors.affiliation: a Genetics Program , Michigan State University , East Lansing , MI , USA.
authors.forename: Evin
authors.initials: E
authors.lastname: Hildebrandt
authors.forename: John R
authors.initials: JR
authors.lastname: Dunn
authors.forename: Hans H
authors.initials: HH
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001284:Atrophy / Q000662:veterinary; D002645:Chickens / Q000276:immunology*; D004265:DNA Helicases / Q000235:genetics / Q000276:immunology*; D019915:DNA Primase / Q000235:genetics / Q000276:immunology*; D025922:Mardivirus / Q000276:immunology* / Q000472:pathogenicity; D008380:Marek Disease / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D022501:Marek Disease Vaccines / Q000235:genetics / Q000276:immunology; D017354:Point Mutation; D011201:Poultry Diseases / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D022501:Marek Disease Vaccines; D014764:Viral Proteins; D019915:DNA Primase; D004265:DNA Helicases