Translational regulation of human adenovirus gene expression

Human adenovirus (Ad) grows efficiently in most cultured human cells (HeLa) but grows poorly in cell lines derived from African green monkey kidney cells (CV-1). During abortive Ad infections of CV-1 cells, expression of the virally encoded fiber protein is blocked at the translational level. Ad2$\sp+$ND5 is a hybird virus in which a nonessential region of the adenovirus genome has been deleted and a portion of the SV40 genome inserted. The SV40-specific 42kd protein produced by Ad2$\sp+$ND5 is also regulated in a posttranscriptional manner similar to that of the Ad fiber protein. The block to replication of these viruses can be overcome by culture of CV-1 cells under modified conditions, by coinfection with an Ad host range (hr) mutant, or by coinfection with simian virus 40 (SV40). Fiber and the 42kd protein are efficiently synthesized during the resulting permissive infections. Correlated with a productive infection and efficient synthesis of fiber protein is an alteration in the splicing pattern of fiber message such that 10 to 25 percent of fiber messages contain the x" or "y" ancillary leader in addition to the tripartite leader common to all late viral messages. In contrast, during abortive infections very little of the fiber mRNA carries either ancillary leader, suggesting that these sequences may be necessary for efficient translation. The translational activity of each class of fiber message was assessed. The presence of the "y" leader in productively infected cells increases the rate of initiation. Elongation is similar on all fiber messages in productively infected cells; however, the rate of elongation of these messages is about threefold slower in abortively infected cells. This reduced elongation is specific for fiber. The similar distribution of fiber mRNAs on polysomes in both infections suggests that initiation must also be partially blocked in abortive infections. Since the majority of the fiber mRNA even in productive infections do not contain the ancillary leaders, the initiation and elongation defects in the abortive infection cannot be fully explained by the absence of these leaders. Therefore, other factors in the infected cell must be influencing the rate of translation.