Animal Retroviruses

The first image of feline leukemia virus (FeLV) reveals two particles enclosed in a vesicle (x160,000)

Since the discovery of feline leukemia virus (FeLV) by Bill Jarrett and colleagues in 1964, the University of Glasgow has maintained an active and productive research programme in retrovirology. Pioneering studies into the transduction of cellular proto-oncogenes by FeLV, the aetiology of ovine pulmonary adenocarcinoma (OPA) and the mechanisms of natural resistance to Jaagsietke Sheep Retrovirus (JSRV) infection, and the identification of the cellular receptors for the feline immunodeficiency virus (FIV), have yielded valuable insights into virus-host interactions.

CVR researchers are now exploring the cellular origins of OPA-associated tumours, asking whether they are derived from bronchio-alveolar epithelial stem cells and defining the mechanism of tumorigenesis. A central aim of the FIV research programme is to understand the phenomenon of vaccine-induced enhancement of infection, a phenomenon that led to the premature termination of the phase III HIV vaccine (STEP) trial. Our knowledge of FIV vaccine-induced enhancement of infection is being used to design vaccine immunogens and regimes that will confer a protective and not enhancing immune response.

Integration is a fundamental step in the retroviral replication cycle and a major factor in the oncogenic activity of many retroviruses. This phenomenon has been exploited extensively in many laboratories to identify genes relevant to cancer and other selectable phenotypes. At the CVR we have used this approach to identify the Runx genes as novel targets for retroviral activation. Unusually these genes can function as oncogenes or tumour suppressors and at the CVR we have elucidated this dualistic role and the interaction of Runx pathways with Myc, p53 and cancer failsafe processes.

More than four decades after the discovery of FeLV, model systems are now being developed by CVR scientists that utilise FeLV and its derivatives as probes to identify genes and pathways involved in human cancer stem cell phenotype, tumour progression and chemo-resistance.

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