In the 1950's, attempts were made to adapt human adenoviruses to growth in monkey tissues for use in the production of vaccines. However, human adenovirus infection of monkey cells was found to be abortive, and the yield of infectious adenovirus did not exceed input levels. In contrast, when monkey cells were superinfected with SV40, adenovirus replication appeared to proceed normally through all steps, and the yield of adenovirus was increased by 103-105 fold over that in the abortive infection. The phenomenon of increasing adenovirus replication in monkey cells by superinfection with SV40 was called enhancement. For several years enhancement has been studied as a model of reversible host range restriction and the interaction of viral genomes. In addition, it was hoped that the study of restricted replication would provide information about the normal replicative cycle, in much the same way that the study of inborn errors of metabolism has contributed to knowledge of normal metabolic pathways. The authors' approach to this system has been to examine each step in adenovirus replication as it is known to occur in permissive human cells and to see if this process is carried out efficiently in the nonpermissive monkey cell. This paper discusses the evidence that the block to efficient replication is at a step following transcription of mRNA and, most probably, consists of a defect in the association of late RNA species with polyribosomes. This defect, in turn, interrupts the translation of late viral structural proteins. In addition, recent experiments indicate that adenovirus can produce a latent infection in monkey cells, possibly involving integration of viral DNA into host genome, and that this latent infection can be enhanced by SV40 for at least 30 days after initial infection. Therefore, the enhancement system also appears to serve as a model of the activation of latent or subclinical infection.
ASJC Scopus subject areas
- Molecular Biology