title: A detailed molecular analysis of complete bovine leukemia virus genomes isolated from B-cell lymphosarcomas.
abstract: It is widely accepted that the majority of cancers result from multiple cellular events leading to malignancy after a prolonged period of clinical latency, and that the immune system plays a critical role in the control of cancer progression. Bovine leukemia virus (BLV) is an oncogenic member of the Retroviridae family. Complete genomic sequences of BLV strains isolated from peripheral blood mononuclear cells (PBMC) from cattle have been previously reported. However, a detailed characterization of the complete genome of BLV strains directly isolated from bovine tumors is much needed in order to contribute to the understanding of the mechanisms of leukemogenesis induced by BLV in cattle. In this study, we performed a molecular characterization of BLV complete genomes from bovine B-cell lymphosarcoma isolates. A nucleotide substitution was found in the glucocorticoid response element (GRE) site of the 5' long terminal repeat (5'LTR) of the BLV isolates. All amino acid substitutions in Tax previously found to be related to stimulate high transcriptional activity of 5'LTR were not found in these studies. Amino acid substitutions were found in the nucleocapsid, gp51 and G4 proteins. Premature stop-codons in R3 were observed. Few mutations or amino acid substitutions may be needed to allow BLV provirus to achieve silencing. Substitutions that favor suppression of viral expression in malignant B cells might be a strategy to circumvent effective immune attack.
authors.affiliation: Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo 11400, Uruguay. cristina@cin.edu.uy.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Moratorio
authors.forename: Sabrina
authors.initials: S
authors.lastname: Fischer
authors.forename: Sergio
authors.initials: S
authors.lastname: Bianchi
authors.forename: Lorena
authors.initials: L
authors.lastname: Tomé
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Rama
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Obal
authors.forename: Federico
authors.initials: F
authors.lastname: Carrión
authors.forename: Otto
authors.initials: O
authors.lastname: Pritsch
authors.forename: Juan
authors.initials: J
authors.lastname: Cristina
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D016583:Enzootic Bovine Leukosis / Q000821:virology*; D016679:Genome, Viral; D001909:Leukemia Virus, Bovine / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000662:veterinary* / Q000821:virology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000662:veterinary; D016415:Sequence Alignment / Q000662:veterinary