An Adenovirus Type 3 Host Range Variant with Mutations in the E1a and E3 Early Gene Regions

Abstract

A spontaneous variant of adenovirus (Ad) type 3 (subgroup B) was identified, which did not grow in HeLa cells, but grew in 293 cells with a large plaque morphology. The variant (Ad3var100) had a defect in the the early gene region E1a; it could grow in cells that supplied E1a functions and was complemented for growth in HeLa cells by Ad5 wild-type (subgroup C) but not by the E1a deletion mutant Ad5dl312. It also bore a deletion of some 1.5 kb in the E3 region. The loss of these sequences conferred on the variant the ability to inhibit Ad5 wild-type virus, although was dominant over the variant. Notransdominance was seen between wild-type Ad3 wild-type Ad3 and Ad5. The E1a mutation was placed in a wild-type background and this E1 a mutant had the host range properties of the variant, but did not retain the larger plaque morphology and was not dominant over Ad5. The E3 mutation was separated from the E1a lesion by marker rescue; the resulting E3 mutant retained dominance over Ad5, grew in HeLa cells and had a plaque morphology intermediate between wild-type and variant.