The ability of pseudorabies virus to grow in different hosts is affected by the duplication and translocation of sequences from the left end of the genome to the UL-US junction

Pseudorabies virus is a herpesvirus which has a class 2 genome. However, under certain growth conditions it acquires a genome with class 3-like characteristics. In these variants, the leftmost sequences of the long (L) component of the viral genome have been duplicated and translocated to the right of the L component next to the short (S) component, resulting in an L component that is bracketed by inverted repeats. Consequently, the L component can invert and is found in two orientations relative to the S component. The translocation is accompanied invariably by a deletion of sequences that are normally present in the wild-type genome at the right end of the L component. The virion variants with an invertible L component have a growth advantage over wild-type virus in chicken embryo fibroblasts and chickens; they also have a growth disadvantage in mice or rabbit kidney cells. The changed growth characteristics of the variants reside entirely in the changed structure of the junction between the S and L components. Replacement of that region of the DNA with wild-type sequences restores the wild-type phenotype. To determine whether the modified growth characteristics of the variants are related to the translocation or to the deletion, mutants that have a deletion or that have a deletion as well as a translocation similar to those observed in the variants were constructed, and the growth characteristics of these mutants were determined. We show that the modified growth characteristics of the mutants with an invertible L component can be attributed to the translocation of the leftmost terminal sequences of the genome next to the inverted repeat; they are not related to the deletion of the sequences normally present at the right end of the L component. The translocation of the leftmost 325 bp of the genome is sufficient to confer upon the virus the modified cell-type-specific growth characteristics. Furthermore, the modified growth characteristics are contingent upon the presence of 68 bp spanning the internal junction between the L and S components.