DNA sequence of the HPV-16 E5 ORF and the structural conservation of its encoded protein

Abstract

Infection of cervical epithelium by human papillomavirus type 16 (HPV-16) appears to be closely associated with the development of cervical dysplasia and carcinoma. By inference from genetic and biochemical studies of the bovine papillomavirus, the E5 ORF of the human papillomaviruses is anticipated to encode a “transforming” protein. In an effort to compare the E5 ORF of HPV-16 with other human papillomaviruses and bovine papillomavirus, we sequenced this region from a new isolate of HPV-16 which was derived from extrachromosomal viral DNA within a premalignant cervical lesion (cervical intraepithelial neoplasia, grade III, or CIN III). In addition, we also sequenced the original isolate of HPV-16 (derived from integrated viral DNA by Durst et al. [Proc. Nad. Acad. Sci. USA 80, 3812–3815 (1983)] and sequenced by Seedorf et al. [Virology 145,181–185 (1985)]. Both HPV-16 isolates contained an additional nucleotide (T) at bb 3906. This nucleotide addition caused a frameshift in the E5 ORF such that it now contains an initiation codon at bp 3849; the frameshift also alters the predicted E5 NHZ terminus but retains the original COOH half of the protein. E5 proteins encoded by several HPVs which infect the genital region (e.g., types 6, 11, 16, 18, 33) exhibit a conserved trimodal hydrophobic structure, but not a conserved amino acid sequence.