Genomic Difference of Herpesvirus of Turkeys at Low and High Passage Levels in Culture of O1 and FC126 Strains

Abstract

Serial passages in culture of herpesvirus of turkeys resulted in structural genomic changes at the regions common to two virus strains with loss of their protective ability against Marek's disease.Herpesvirus of turkeys (HVT) or Marek's disease virus (MDV) serotype 3 have been used for vaccination against Marek's disease (MD), a highly contagious lymphoproliferative disease, caused by MDV serotype 1 (MDV1). Although most of the virus-specific polypeptides of MDVl and HVT have cross-reactive epitopes (10,11,17), the two viruses have no significant DNA homology except in a restricted portion of their genomes (4,12,14). However, Southern blot hybridization under less stringent conditions indicated that regions with weak homology were distributed over most of these two viral genomes (3, 6). A similar relationship exists between the DNAs of MDV type 2 and MDV 1 or HVT (8). The homologous DNA regions found by low-stringency hybridization were located at the corresponding positions on the restriction enzyme maps of MDV1 and HVT DNAs, indicating the collinear relationship between these two virus genomes (9). The genome structure of both MDVl and HVT consists of a long unique region (UL) and a short unique region (Us) bounded by inverted repeats (1).Serial passages of HVT over 70 times in cultured cells resulted in a loss of their ability to protect chickens from MD (13,18,19). The nonprotective variants of HVT did not replicate in vivo in chickens, but replicated well in cultured cells. Since serial passages of the oncogenic MDV 1 in cultured cells resulted in a structural change of the viral DNA with simultaneous loss of oncogenicity (2,4,5,7,15,16), the structure of HVT DNA may also change during its serial passages of HVT in cultured cells. However, very little is known about the variable regions on the genomes of various HVT isolates. In this study, we attempted to locate the common regions on the HVT genome which differed in structure between low-passaged, 871