The oncogenic retrovirus Rous sarcoma virus (RSV) is an excellent system for investigating cell-specific differences that result in permissive and nonpermissive retroviral infections in avian and mammalian cells, respectively. It is also an important system for studying expression of the viral oncogenes. Differences in RSV RNA splicing, stability, and transport in permissive avian fibroblasts and nonpermissive mammalian cells will be studied. A number of in vivo DNA transfection and virus infection assays will be used, to study several cis elements within the RSV genome that may represent binding sites for cellular proteins involved in the transport of unspliced viral RNA from the nucleus to the cytoplasm. In vitro splicing assays will be used to characterize avian fibroblast nuclear factors that interact with a cis site upstream of the src 3' splice site and specifically inhibit splicing at this splice site. Additional nonsense codon mutations will be constructed within the src gene coding region to determine how these mutations act to specifically reduce src mRNA levels. The information obtained in the proposed studies will add to knowledge of the role of RNA processing, stability and transport in the maintenance of acute and latent retroviral infections. Because retroviruses bypass the normal requirements for complete splicing prior to transport, it will also add to the understanding of how cellular RNA,processing and transport are regulated.
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