Isolation of type 5 adenovirus mutants with a cold-sensitive host range phenotype: Genetic evidence of an adenovirus transformation maintenance function

We have isolated host range mutants of type 5 adenovirus which possess a cold-sensitive host range phenotype. These mutants grow well on 293 cells at 32.5° and 38.5°, and on HeLa cells at 38.5° but show restricted growth upon HeLa cells at the low temperature. Complementation and recombination tests with prototype hr and dl mutants of type 5 assign these new mutants to group I, mapping in early region 1A (ElA), and group II, mapping in early region 1B (ElB). The ElA mutants possess a cold-sensitive transformation phenotype, and the results of temperature-shift analyses of transformation and transformed cell phenotype provide strong genetic evidence that an E1A gene function is required either directly or indirectly for maintenance of transformation. The ElB mutants are effectively transformation defective at both high and low temperatures, but hr transformants established at 38.5° do show a cold-sensitive phenotype. Thus, an ElB gene function may be involved in both initiation and maintenance.