TRANSFORMATION BY HUMAN CMV

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Human cytomegalovirus (CMV) infection has been associated with several neoplastic diseases, including prostatic carcinoma, adenocarcinoma of the colon, cervical carcinoma, and Kaposi's sarcoma. The morphological transforming region II (mtrII) of CMV Towne has been localized to a 980 base-pair fragment containing three putative open reading frames (ORFs) of 79, 83, and 34 amino acids (aa). Noncoding DNA sequence elements which have the potential to form stem-loop structures were also observed within mtrII. To determine what elements within CMV Towne mtrII are important in transformation, colinear regions in other CMV strains (AD169 and Tanaka) were isolated and a comparison of transforming potential was performed. The results indicated that the 2.2-kilobase colinear region in strain AD169 was transforming, whereas the colinear mtrII region in strain Tanaka showed significantly less transforming potential. Analysis of the nucleotide sequence data of these colinear regions revealed the presence of the 79-aa ORF in strains Towne and AD169 and its absence in strain Tanaka. In addition, Bgl II-digested Towne mtrII, which was cleaved within the 79-aa ORF, was shown to display significantly reduced transforming potential. Since the 83 and 34-aa coding sequences were interrupted in both the transforming AD169 colinear region and the nontransforming Tanaka strains, these ORFs were thought not to be important in transformation. Analysis of the stem-loop structures within each of the mtrII colinear regions did not reveal significant changes among the transforming and nontransforming colinear fragments. Thus, the comparative data indicate an important role for the 79-aa ORF in transformation.