Tumorigenic transformation induced by a specific fragment of DNA from herpes simplex virus type 2

Transfection of Syrian hamster embryo cells with limit digests of Bgl II-, Hpa I-, or Bgl II/Hpa I-cleaved DNA from herpes simplex virus type 2 (strain S-1) but not with salmon sperm DNA resulted in the appearance of refractile, morphologically altered cells at a frequency of 10(-5)/0.005 microgram of viral DNA within two to four passages. Transformed lines manifested reduced serum requirement and anchorage-independent growth and were tumorigenic in newborn hamsters. They expressed ICP10, a viral protein immunologically identical to the cervical-tumor-associated AG-4 antigen. Transforming activity was localized in the 16.5 x 10(6)-dalton Bgl II/Hpa I double-digest fragment CDs-1, which exhibited sequence homology to the Bgl II/Hpa I fragment CD of DNA from herpes simplex virus type 2 strain 333, mapping between coordinates 0.43 and 0.58 on the physical map of strain 333 DNA. This fragment, CD333, was also shown to induce neoplastic transformation.