Antiviral restriction factor transgenesis in the domestic cat. Studies of the domestic cat have contributed to many scientific advances, including the present understanding of the mammalian cerebral cortex. A practical capability for cat transgenesis is needed to realize the distinctive potential of research on this neurobehaviorally complex, accessible species for advancing human and feline health. For example, humans and cats are afflicted with pandemic AIDS lentiviruses that are susceptible to species-specific restriction factors. Here we introduced genes encoding such a factor, rhesus macaque TRIMCyp, and eGFP, into the cat germline. The method establishes gamete-targeted transgenesis for the first time in a carnivore. We observed uniformly transgenic outcomes, widespread expression, no mosaicism and no F1 silencing. TRIMCyp transgenic cat lymphocytes resisted feline immunodeficiency virus replication.
This capability to experimentally manipulate the genome of an AIDS-susceptible species can be used to test the potential of restriction factors for HIV gene therapy and to build models of other infectious and noninfectious diseases. – Prof. Eric M Poeschla; Our research interests are in the molecular pathogenesis of HIV disease/AIDS and in uses of lentiviral vectors in human gene therapy. Lentiviral Vectors; HIV Disease Pathogenesis. We investigate lentivirus biology to develop novel gene transfer vectors suitable for human gene therapy and to elucidate mechanisms of lentiviral (HIV) disease pathogenesis. Lentiviruses such as HIV-1 differ from other retroviruses in their ability to infect non-dividing cells in vivo; for example, HIV-1 infects terminally differentiated tissue macrophages in vivo. Lentiviral vectors exploit this ability to achieve stable integration in non-dividing cells. HIV-based and feline immunodeficiency virus (FIV)-based lentiviral vectors are being studied in our laboratory. Collaborations have also been developed with other investigators at Mayo and elsewhere to investigate lentiviral vector gene therapy. Several individuals in the laboratory are using the eye as a model system, with a focus on glaucoma gene therapy.We are interested in the molecular basis of HIV disease pathogenesis, and are investigating functional interatctions of integrase and other HIV-1 proteins with cellular factors (LEDGF/p75, HRP-2), and interactions of Gag proteins and viral RNA in genome packaging.Sources: PubMed National Institutes of Health, & Department of Molecular Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota.
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