Ruth Fulton

Feline leukaemia virus: generation of pathogenic and oncogenic variants.

Although feline leukaemia virus (FeLV) is a common and potent pathogen of the domestic cat, neoplastic disease is a relatively rare outcome of the virus-host interaction and generally occurs after a long latent period (Hardy et al. 1976; Jarrett 1984). For these reasons, it has been customary to classify FeLV as a chronic leukaemogenic retrovirus and to place the acute transforming C-type retroviruses in a separate subclass. In our view, this classification has been unhelpful since it obscures the fact that acute transforming retroviruses invariably arise from the chronic leukaemogenic variety. Moreover, there is mounting evidence that terminal diseases which develop in FeLV-infected cats are induced by variant genomes that arise de novo. In this review, we discuss the origins of FeLV variants and briefly consider their roles in disease.

Nucleotide and predicted peptide sequence of feline interferon-gamma (IFN-gamma)

Interferon gamma is a pleiotropic cytokine which is now recognised as an important modulator of the immune response. We now report the cloning and sequencing of feline interferon gamma cDNA which was generated by the polymerase chain reaction. At the nucleotide level feline ifn-gamma shares 78% and 63% homology with human and murine cDNA equivalents. At the amino acid level the feline IFN-gamma shares 63% and 43% homology with human and murine homologs respectively.

The fit -1 common integration locus in human and mouse is closely linked to MYB

The fit-1 locus was originally identified as a common insertion site for feline leukemia virus (FeLV) in thymic lymphosarcomas induced by FeLV-myc recombinant viruses, suggesting that it harbors a gene that cooperates with Myc in T-cell leukemogenesis. We have previously mapped the fit-1 locus to feline Chromosome (Chr) B2. We have now identified conserved sequences that allow the mapping of the murine homolog using the European Interspecific Backcross (EUCIB). This shows that fit-1 is located on mouse Chr 10, 1cM proximal to Ahi-1, a murine retroviral integration locus that is closely linked to Myb. Moreover, the physical linkage to MYB is maintained in the human genome, as shown by cloning of the human homolog of fit-1 from a Chr 6 cosmid library and a series of overlapping PAC clones. Generation of a contig map around the human homolog of fit-1 reveals that it is approximately 100-kb upstream of MYB. In addition to fit-1 and Ahi-1, two other common insertion sites, Mis-2 and Mml-1, have also been mapped adjacent to Myb on mouse Chr 10. Previous analysis of tumors carrying insertions at fit-1, Mml-1, Mis-2 and Ahi-1 showed no obvious abnormalities in Myb expression. However, the cluster of viral insertion loci in this region suggests either the presence of a closely linked activation target or that subtle effects on Myb have been overlooked.

Cloning and sequence of the feline max, and max 9 transcripts

Max is the recently discovered heterodimeric partner of the human myc oncogene product. In this report we describe the cloning and sequencing of two differentially spliced transcripts of the feline max gene. Previously published data have shown both myc and max to be highly conserved amongst species, and indeed there is a 100% homology between feline max and max, while the murine equivalent myn is 98% homologous at the amino acid level, with the nucleotide sequences showing a similarity of 98% and 95% respectively.

Viral transduction of host genes in naturally occurring feline T-cell leukaemias: transduction of myc and a T-cell antigen receptor beta-chain gene.

Feline leukaemia virus has been a particularly useful tool in cancer research since many of the naturally occurring tumours associated with this virus group have yielded recombinant retroviruses containing hostderived oncogenic information. The prevalence of transduction as an oncogenic mechanism was seen first in multicentric fibrosarcoma, a relatively rare tumour in FeLV-infected cats (Hardy et al. 1982; Besmer 1984). In a significant percentage of cases of this disease, oncogene-containing feline sarcoma viruses have been identified. More recently, we and others have found that in the more common FeLV-associated neoplasm, thymic lymphosarcoma, viral capture of the c-myc gene can occur (Neil et al. 1984; Levy et al. 1984; Mullins et al. 1984). Since the oncogenes carried by feline sarcoma viruses do not include myc, these reports provided the first evidence that myc may be a target for oncogenic activation by FeLV.