The Kinetics of Synthesis of Early Viral Proteins in KB Cells Infected with Wild-type and Transformation-defective Host-range Mutants of Human Adenovirus Type 5

We have studied the kinetics of early adenovirus type 5 (Ad5) protein synthesis during lytic infection of KB cells by wild-type (wt) and transformation-defective host-range (hr) mutants. Proteins encoded within four early regions were studied: early region 1A (E1A: 1.5 to 4.5 map units, mu), E1B (4.5 to 11.2 mu), E2A (61.6 to 74.9 mu), and E4 (91.4 to 99.1 mu). Synthesis of E1A products, the first to appear during wt lytic infection, was detectable within 2 h after injection, reached a peak within the next hour, then declined to very low levels by 7 h post-infection. Synthesis of E2 and E4 proteins began at about 3 h post-infection, was maximal by 6 h and thereafter declined sharply. The E1B 19K and 58K proteins were first detected around 3 h post-infection and, after reaching maximal levels of expression by 8 h, declined to lower levels by 12 h post-infection. Infections with the E1A mutant hr3 were characterized by greatly depressed levels of early expression of E1B, E2 and E4 polypeptides but protein synthesis from these regions appeared to recover at late times. The pattern of expression exhibited by the E1B mutant hr6 revealed delayed and reduced levels of expression of E1B, E2 and E4 protein synthesis but increased levels of E1A protein synthesis. These results are consistent with the reported role of E1A gene products in the activation of early gene expression and, in addition, suggest that a function encoded in E1B may also influence the expression of Ad5 early genes at early and late times.