Genetic Evidence for a Temperature-Sensitive Lesion in the Adenovirus 7 Region of the PARA Genome

Abstract

It has previously been shown that the helper adenovirus (Ad) present in the defective Ad 7-SV40 hybrid population is temperature-sensitive (ts) for replication in human cells. This study has shown that the replication of the defective hybrid virus (PARA) in green monkey kidney cells is also restricted at 40.5 percent. Complementation tests between the parental or transcapsidant PARA populations and SV40 or various Ad serotypes revealed that the ts lesion is located in the Ad region of the hybrid genome. Wild-type (wt) Ad type 7 and Ad type 21 were able to complement the replication of PARA while Ad type 31 was unable to do so. Complementation was more efficient after the PARA genome was transcapsidated to the wt isolates of helper Ad than during multiple infections with the parental hybrid population. The SV40 function which complements the replication of human adenoviruses in simian cells is not expressed by PARA at the nonpermissive temperature. However, the ts lesion does not affect the expression of SV40 functions coded for by PARA under other conditions, i.e., complementation of the replication of human adenoviruses in transformed monkey cells, and synthesis of T antigen in lytically infected or transformed cells. Although the exact nature of the mutated Ad 7 gene product is unknown, heat inactivation data suggest that it may be a structural protein.