Mutants dl312, d1314, hrl, and hr3 with mutations in region ElA of adenovirus type 5 were defective for the induction of cell cycle abnormalities detectable by flow cytometry, cell DNA replication, thymidine kinase production, and chromosome aberrations and did not synthesize the viral DNA-binding protein (E2A) in rat cells. dl311, a leaky ElA mutant, induced cell cycle effects at high multiplicity in only one of three experiments, and synthesized the DNA-binding protein. hr7 (E1B) gave a wild-type response in all tests. d1313 was also positive in all tests, although it induced fewer polyploid cells than did wild-type virus, probably because of the leftward extension of the d1313 E1B deletion into ElA. sub315 and sub316, with mutations which also span the E1A-E1B border, synthesized DNAbinding protein, but caused no cell cycle alterations detectable by flow cytometry in rat or mouse cells. Although the participation of other viral early regions cannot be completely excluded, our results suggest that alteration of cell cycle progression is a direct effect of EtA unrelated to its control of other viral early regions, and may be the function of ElA in transformation.

CELO virus (fowl adenovirus 1) contained three core polypeptides of molecular weights 20,000, 12,000, and 9,500. The core was similar to that of human adenoviruses, with some evidence of compact subcore domains. Micrococcal nuclease digestion of CELO virus cores produced a smear of DNA fragments of gradually decreasing size, with no nucleosome subunit or repeat pattern. Moreover, when digested cores were analyzed without protease treatment, there was again no evidence of a nucleosome substructure; neither DNA fragments nor core proteins entered a 4% polyacrylamide gel. The organization of the core is thus quite unlike that of chromatin. Restriction endonuclease analysis of the DNA from digested cores showed that the right end was on the outside of the core. We suggest that adenovirus DNA is condensed into the core by cross-linking and neutralization by the core proteins, beginning with the packaging sequence at the center of the core and ending with the right end of the DNA on the outside. Adenoviruses contain an internal core that consists of the viral DNA and the virus-coded, basic core proteins. In human adenovirus, there are two prominent arginine-rich core proteins, the major core protein (polypeptide VII) and the minor core protein (polypeptide V). Of the two, the major core protein is more tightly associated with the viral DNA (4, 14, 15). A third virion polypeptide, designated [i, which is very small and very rich in arginine, may also be associated with the viral DNA (25). The adenovirus terminal protein (43, 44) is covalently linked to the 5' ends of the viral genome. The structure of the adenovirus core has been investigated by electron microscopy, and several different morphological structures have been proposed. Brown et al. (4) proposed that the core was organized into 12 morphological subunits, each under a vertex of the capsid. However, Nermut (38, 39) suggested that the viral DNA was wrapped around a helical filament composed of the major core protein, and that the resulting nucleoprotein was packed into six rodlike elements.