title: A mutant form of the tax protein of bovine leukemia virus (BLV), with enhanced transactivation activity, increases expression and propagation of BLV in vitro but not in vivo.
abstract: In a previous study, we identified an interesting mutant form of the Tax protein of bovine leukemia virus (BLV), designated D247G. This mutant protein strongly transactivated the long terminal repeat of BLV and was also able to transactivate the cellular proto-oncogene c-fos. This finding suggested that BLV that encode the mutant protein might propagate and induce lymphoma more efficiently than wild-type BLV. To characterize the effects of the strong transactivation activity of the mutant Tax protein, we constructed an infectious molecular clone of BLV that encoded D247G and examined the replication and propagation of the virus in vitro and in vivo. Cultured cells were transfected with the wild-type and mutant BLV, and then levels of viral proteins and particles and the propagation of viruses were compared. As expected, in vitro, mutant BLV produced more viral proteins and particles and was transmitted very effectively. We injected the wild-type and mutant BLV into sheep, which are easily infected with BLV, and monitored the proportion of BLV-positive cells in the blood and the expression of BLV RNA for 28 weeks. By contrast to the results of our analyses in vitro, we found no significant difference in the viral load or the expression of viral RNA between sheep inoculated with wild-type or mutant BLV. Our observations indicate that the mutant D247G Tax protein does not enhance the expansion of BLV and that there might be a dominant mechanism for regulation of the expression of BLV in vivo.
authors.affiliation: Retrovirus Research Unit, RIKEN, Wako, Saitama 351-0198, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tajima
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Shin-Nosuke
authors.initials: SN
authors.lastname: Takeshima
authors.forename: Satoru
authors.initials: S
authors.lastname: Konnai
authors.forename: Shan Ai
authors.initials: SA
authors.lastname: Yin
authors.forename: Shinobu
authors.initials: S
authors.lastname: Watarai
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Misao
authors.initials: M
authors.lastname: Onuma
authors.forename: Kosuke
authors.initials: K
authors.lastname: Okada
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aida
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016356:Gene Products, tax / Q000502:physiology*; D006801:Humans; D001909:Leukemia Virus, Bovine / Q000502:physiology*; D009154:Mutation; D000090063:Proto-Oncogene Mas; D012367:RNA, Viral / Q000097:blood; D012756:Sheep; D015533:Transcriptional Activation; D014162:Transfection; D019562:Viral Load
chemical_list: D016356:Gene Products, tax; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012367:RNA, Viral