Transduction of Notch2 in feline leukemia virus-induced thymic lymphoma

• Published in: Journal of Virology Vol. 70; no. 11; pp. 8071 - 8080
• Main Authors: Rohn, J.L. (University of Washington, Seattle, WA.), Lauring, A.S, Linenberger, M.L, Overbaugh, J
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01-11-1996
• Subjects: ADN RECOMBINADO; ADN RECOMBINE; Amino Acid Sequence; Animals; ARN; Base Sequence; Cat Diseases - virology; Cats; Cell Line; CHAT; CHIMIORECEPTEUR; Cloning, Molecular; COMPOSICION QUIMICA; COMPOSITION CHIMIQUE; DNA, Viral; ENFERMEDADES INMUNOLOGICAS; EXPERIMENTACION IN VIVO; EXPERIMENTATION IN VIVO; feline leukemia virus; GATO; GENE; Gene Rearrangement; GENES; GENETICA; GENETIQUE; GENOMAS; GENOME; Genome, Viral; GLANDE THYMUS; GLANDULA DEL TIMO; INFECCION EXPERIMENTAL; INFECTION EXPERIMENTALE; LEUCEMIA; LEUCEMIE; Leukemia Virus, Feline - genetics; LINFOMA; Lymphoma - veterinary; Lymphoma - virology; LYMPHOME; MALADIE IMMUNOLOGIQUE; Molecular Sequence Data; MUTACION; MUTATION; PROTEINAS; PROTEINE; Proviruses; QUIMIORECEPTORES; Rats; Receptor, Notch2; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Cell Surface - genetics; RECOMBINACION; RECOMBINAISON; Recombination, Genetic; Retroviridae Infections - veterinary; Retroviridae Infections - virology; RNA, Viral - analysis; SECUENCIA NUCLEOTIDICA; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; SEQUENCE NUCLEOTIDIQUE; Thymus Neoplasms - veterinary; Thymus Neoplasms - virology; Transfection; Tumor Virus Infections - veterinary; Tumor Virus Infections - virology; VIRUS DE LOS ANIMALES; VIRUS DES ANIMAUX
• ISSN: 0022-538X; 1098-5514
• DOI: 10.1128/jvi.70.11.8071-8080.1996

Feline leukemia virus (FeLV) is thought to induce neoplastic diseases in infected cats by a variety of mechanisms, including the transduction of host proto-oncogenes. While FeLV recombinants that encode cellular sequences have been isolated from tumors of naturally infected animals, the acquisition of an unrelated host gene has never been documented in an experimental FeLV infection. We isolated recombinant FeLV proviruses encoding feline Notch2 sequences from thymic lymphoma DNA of two cats inoculated with the molecularly cloned virus FeLV-61E. Four recombinant genomes were identified, three in one cat and one in the other. Each had similar but distinct transduction junctions, and in all cases, the insertions replaced most of the envelope gene with a region of Notch2 that included the intracellular ankyrin repeat functional domain. The product of the FeLV/Notch2 recombinant provirus was a novel, truncated 65- to 70-kD Notch2 protein that was targeted to the cell nucleus. This virally encoded Notch2 protein, which resembles previously constructed, constitutively activated forms of Notch, was apparently expressed from a subgenomic transcript spliced at the normal envelope donor and acceptor sequences. The data reported here implicate a nuclear, activated Notch2 protein in FeLV-induced leukemogenesis