Use of Rous Sarcoma Viral Genome to Express Human Fibroblast Interferon

Publisher Summary This chapter discusses the use of Rous sarcoma viral genome to express human fibroblast interferon. The attractiveness of the retroviral genome as a vehicle for the expression of exogenous genes can be attributed primarily to two features. First, the retroviral genome possesses a highly efficient promoter contained within the long terminal repeat (LTR) sequence. The LTR provides a number of functions that are critical to the replication, integration, and expression of retrovirus genomes, including sequences involved in the regulation of transcription. Apart from regulating the expression of the viral genes, the LTR can activate the expression of heterologous DNA sequences. The exogenous gene may provide its own translation initiation and termination signals or use those contained within the viral sequences. The second feature that makes the retroviral genome a potentially useful expression vector concerns the integration of viral DNA into host cell DNA. During the viral infection process, a DNA copy of the viral genome with its LTRs is generated from the viral RNA. This DNA intermediate is integrated into the host chromosomes. The position of the human fibroblast interferon gene inserted into the avian retroviral genome determines, to a large extent, the level of interferon expression by the chimeric DNA. Positioning the interferon gene downstream from the splice acceptor site used for the generation of env messenger RNA (mRNA) is moderately effective in producing active interferon.