A total of 59 cytocidal (cyt) mutants were isolated from adenovirus 2 (Ad2) and AdS. In contrast to the small plaques and adenovirus type of cytopathic effects produced by wild-type cyt+ viruses, the cyt mutants produced large plaques, and the cytopathic effect was characterized by marked cellular destruction. cyt mutants were transformation defective in established rat 3Y1 cells. cyt+ revertants and cyt+ intragenic recombinants recovered fully the transforming ability of wild-type viruses. Thus, the cyt gene is an oncogene responsible for the transforming function of Ad2 and Ad5. Genetic mapping in which we used three Ad5 deletion mutants (d1312, d1313, and d1314) as reference deletions located the cyt gene between the 3' ends of the d1314 deletion (nucleotide 1,679) and the d1313 deletion (nucleotide 3,625) in region ElB. Restriction endonuclease mapping of these recombinants suggested that the cyt gene encodes the region ElB 19,000-molecular-weight (175R) polypeptide (nucleotides 1,711 to 2,236). This was confirmed by DNA sequencing of eight different cyt mutants. One of these mutants has a single missense mutant, two mutants have double missense mutations, and five mutants have nonsense mutations. Except for one mutant, these point mutations are not located in any other known region ElB gene. We conclude that the cyt gene codes for the E1B 19,000-molecular-weight (175R) polypeptide, that this polypeptide is required for morphological transformation of rat 3Y1 cells, and that simple amino acid substitutions in the protein can be sufficient to produce the cyt phenotype.
Most humans in the United States have been infected with BK virus (BKV), a human papovavirus. Because BKV has oncogenic properties, we have investigated whether it may be a cause of human cancer. Basic principles of tumor virology imply that BKV-induced tumors should contain BKV DNA sequences. Therefore, we assayed (by molecular hybridization) DNA The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. express T antigen, and are tumorigenic in hamsters (12,14,15). BKV is related to but distinct from simian virus 40 (SV40) and JC virus, another human papovavirus (18). BKV and SV40 T antigens crossreact strongly (9,12,14,15,19,20) (the SV40 T antigen is believed to be a protein encoded by the SV40 early region and to play a role in SV40-induced cell transformation).Because BKV is widespread in the human population and has oncogenic properties, it is important to determine whether it is a cause of human cancer. To test this, we assayed for BKV DNA sequences in DNA from 166 human tumors and 7 malignant cell lines, using in vitro 32P-labeled BKV DNA (1 to 2 X 108 cpm/,gg) as probe in saturation molecular hybridization reactions. On the basis of studies of transformation and tumorigenesis in animals with papovaviruses and other DNA tumor viruses, tumors induced by BKV would be expected to contain BKV DNA (probably integrated). In this report we describe the preparation and characterization of BKV
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