Multistep transformation by defined fragments of herpes simplex virus type 2 DNA: oncogenic region and its gene product.

Diploid Syrian hamster embryo cells transfected with Bgl II C fragment of herpes simplex virus type 2 DNA acquired a neoplastic phenotype. Cultures transfected with its left-hand 64% subclone EcoRI/HindIII fragment AE (0.419-0.525 map unit) grew into established but nontumorigenic lines. Transfection of EcoRI/HindIII AE-immortalized cells with a 4.4-kilobase Sac I/BamHI subfragment within BamHI E (0.554-0.584 map unit; overlaps the right-hand 16% of Bgl II C) converted them to tumorigenicity. The 4.4-kilobase subfragment encodes a 144-kDa protein immunologically and structurally similar to an infected cell protein designated ICP 10. DNA extracted from cells transformed with the 4.4-kilobase subfragment exhibited discrete hybridizing bands homologous to BamHI E fragment. Monoclonal antibody to ICP 10 precipitated a 144-kDa protein from the transformed cells and stained them in immunofluorescence. A tumor derivative established with the transformed cells did not stain with this antibody, but approximately equal to 25% of the cells stained with a monoclonal antibody to c-myc protooncogene products.