ALTERED HOST-RANGE PHENOTYPE OF THE TRANSFORMATION-DETECTIVE AD12 MUTANT CS-1 IS DUE TO DELETIONS IN THE E1 REGION

Although it grows well in bulk infection, human adenovirus type 12 (Ad l2) does not plaque efficiently in Vero cells of simian origin. After long-term passage of the virus or after transfection of Ad12 DNA into these cells, however, transformation-defective, host-range mutants giv ing high plaque yields in Vero cells were isolated. The original mutan ts have deletions in both Ela and Elb as well as additions of viral se quences at the right terminus of the genome. We have constructed a rec ombinant virus (Ad12d169) carrying both El alterations of the original mutant CS-1 on the Ad12 wild-type background. Another mutant (Ad12mut 2) has additional sequences at the right terminus and an intact El reg ion. In plaque assays mutant virus Ad12d169 carrying Ela deletions has an about thousandfold higher efficiency in Vero cells than Ad12wt and Ad12mut2, mapping the enhanced replication in Vero cells to the delet ions in E1. Mechanical models for the influence of the E1 deletions, f or example by up-regulation of the E2-encoded DNA-binding protein, are discussed to explain the efficient replication of mutant adenoviruses in Vero cells under plaque assay conditions.