Synthesis of viral DNA and late capsid protein L1 in parabasal spinous cell layers of naturally occurring benign warts infected with human papillomavirus type 1

We investigated human papillomavirus type 1 (HPV1)-specific transcription, viral DNA replication, and viral protein expression in naturally occurring benign tumors by in situ hybridization, 5-bromodeoxyuridine (BrdU) incorpor ation, and immunohistochemistry and obtained results different from other H PV-infected benign tumors characterized so far. Moderate amounts of transcr ipts with a putative coding potential for E6/E7, E1, and E2 were demonstrat ed from the first subrabasal cell layer throughout the stratum spinosum and granulosum. In addition very large amounts of E4 and L1 transcripts were p resent in the same epithelial layers. This finding was substantiated by the demonstration of L1 and E4 protein already in the bottom-most spinous cell layer. Furthermore massive amplification of the viral DNA as measured by B rdu incorporation and different methods of in situ hybridization took place in the lowest 5 to 10 suprabasal cell layers. These findings are in contra st to the assumption that late gene expression and viral DNA synthesis are restricted to the more differentiated cell layers of the epithelium and poi nt to differences in the regulation of the vegetative life cycle between di fferent papillomavirus types. (C) 2000 Academic Press.