Tetrasomy is induced by human papillomavirus type 18 E7 gene expression inkeratinocyte raft cultures

We have demonstrated previously that oncogenic human papillomaviruses (HPVs ) induce basal cell tetrasomy in low-grade squamous intraepithelial lesions of the cervix, To identify HPV genes and growth conditions involved in thi s process, we analyzed: (a) organotypic raft cultures of primary human kera tinocytes transfected with whole HPV-18 genomes; and (b) organotypic raft c ultures acutely infected with recombinant retroviruses expressing the HPV-1 8 E6, E7, or Ed/E7 genes from the differentiation-dependent HPV-18 enhancer -promoter. Cultures were examined for HPV DNA by in situ hybridization and for karyotype by interphase cytogenetics. Tetrasomy occurred in the supraba sal strata of raft cultures expressing E7 and Ed/E7 but not in those expres sing Ed alone or in a control culture, These data indicate that suprabasal tetrasomy occurs in association with expression of the E7 gene alone. nasal cell tetrasomy was additionally observed in the raft culture transfected w ith whole HPV-18 genomes, consistent with observations in low-grade squamou s intraepithelial lesions. The distribution of tetrasomic cells in these ra ft cultures may reflect the involvement of additional viral genes or possib ly differences in the pattern of viral oncogene and host gene expression.