IDENTIFICATION AND LOCATION OF HUMAN PAPILLOMAVIRUS TYPE-16 ANTISENSEEARLY PROMOTER AND CHARACTERIZATION OF ANTISENSE RNA

Antisense RNA sequences of various regions of human papillomavirus typ e 16 (HPV 16) were previously found in a number of cervical lesions, b ut the viral or cellular promoter has not been identified. HPV 16 E7 o ncogene antisense transcripts expressed from an antisense promoter in viral DNA were found in the present study by RNase protection assays f or total and cytoplasmic RNA. The antisense promoter for these transcr ipts was located within HPV 16 nt 4030-4230 by deletion analyses. The results also suggested that most of the antisense RNA was relatively s hort. The antisense promoter of HPV 16 was functional for expression o f antisense RNA of a heterologous gene. Antisense-sense double-strande d E7 RNA was detected, and the sense RNA of this duplex was apparently inefficient for splicing or cleavage/poly(A) addition. These results show that HPV 16 can produce early region antisense RNA, which is from a promoter within a defined region of the viral genome. The possible importance of these transcripts for the regulation of episomal HPV 16 gene expression in infected and premalignant lesions and the possible importance of their deregulation for expression in malignant lesions a re discussed. (C) 1997 Wiley-Liss, Inc.