title: Even attenuated bovine leukemia virus proviruses can be pathogenic in sheep.
abstract: Based on a reverse genetics approach, we previously reported that bovine leukemia virus (BLV) mutants harboring deletions in the accessory R3 and G4 genes persist at very low proviral loads and are unable to induce leukemia or lymphoma in sheep, indicating that these R3 and G4 gene sequences are required for pathogenesis. We now show that lymphoma can occur, albeit infrequently (1 case of 20) and after extended periods of latency (7 years). Direct sequencing and reinfection experiments demonstrated that lymphomagenesis was not due to the reversion of the mutant to the wild type. Similar observations with another type of attenuated mutant impaired in the transmembrane protein (TM) YXXL signaling motifs were made. We conclude that the R3 and G4 genes and the TM YXXL motifs are not strictly required for pathogenesis but that their integrity contributes to disease frequency and latency.
authors.affiliation: Molecular and Cellular Biology Laboratory, National Fund for Scientific Research-FUSAGx, 13 avenue Maréchal Juin, 5030 Gembloux, Belgium.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Florins
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gillet
authors.forename: Mathieu
authors.initials: M
authors.lastname: Boxus
authors.forename: Pierre
authors.initials: P
authors.lastname: Kerkhofs
authors.forename: Richard
authors.initials: R
authors.lastname: Kettmann
authors.forename: Luc
authors.initials: L
authors.lastname: Willems
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D002417:Cattle; D002472:Cell Transformation, Viral / Q000235:genetics; D004252:DNA Mutational Analysis; D016583:Enzootic Bovine Leukosis / Q000235:genetics* / Q000821:virology; D001909:Leukemia Virus, Bovine / Q000235:genetics* / Q000472:pathogenicity; D008223:Lymphoma / Q000235:genetics* / Q000662:veterinary / Q000821:virology*; D008565:Membrane Proteins / Q000235:genetics; D017384:Sequence Deletion; D012756:Sheep / Q000821:virology*; D012757:Sheep Diseases / Q000235:genetics* / Q000821:virology*; D013997:Time Factors; D014764:Viral Proteins / Q000235:genetics; D017735:Virus Latency / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D014764:Viral Proteins