Incomplete splicing and deficient accumulation of the fiber messenger RNA in monkey cells infected by human adenovirus type 2

Abstract

Monkey cells are non-permissive hosts for human adenoviruses due to a block in the synthesis of certain late viral proteins. Analysis of the RNA produced in abortively infected monkey cells indicated that the depressed synthesis of many of the late proteins can be ascribed to the reduced concentration of their corresponding mRNAs (Klessig & Anderson, 1975). An exception is the capsid polypeptide, fiber. Fiber RNA concentration is reduced by five- to 20-fold in monkey cells, whereas fiber protein synthesis is depressed by 100 to 1000-fold. Experiments designed to detect defects in the cytoplasmic fiber RNA which would account for its poor translatability showed that the RNA had a normal, capped tripartite leader at its 5′ terminus. However, a large proportion of these molecules contained long sequences between the tripartite leader and the main body which failed to be spliced out of the initial transcript during maturation of the fiber mRNA. Similarly, region 3 RNAs at late times also contained the same long upstream sequences in abortive infections. In contrast, few cytoplasmic fiber or region 3 RNAs from a productive infection with an adenovirus type 2 mutant, which grows lytically in monkey cells, retained such long upstream sequences. The other late RNAs from abortively or productively infected monkey cells had splicing patterns identical to those seen in permissive human cells. These observations suggest a role for RNA splicing in the control of gene expression and may represent an example of limited host range of a virus due to deficient RNA splicing.