title: L233P mutation of the Tax protein strongly correlated with leukemogenicity of bovine leukemia virus.
abstract: The bovine leukemia virus (BLV) Tax protein is believed to play a crucial role in leukemogenesis by the virus. BLV usually causes asymptomatic infections in cattle, but only one-third develop persistent lymphocytosis that rarely progress after a long incubation period to lymphoid tumors, namely enzootic bovine leucosis (EBL). In the present study, we demonstrated that the BLV tax genes could be divided into two alleles and developed multiplex PCR detecting an L233P mutation of the Tax protein. Then, in order to define the relationship between the Tax protein and leukemogenicity, we examined 360 tumor samples randomly collected from dairy or breeding cattle in Japan, of which Tax proteins were categorized, for age at the time of diagnosis of EBL. The ages of 288 animals (80.0%) associated with L233-Tax and those of 70 animals (19.4%) with P233-Tax individually followed log-normal distributions. Only the two earliest cases (0.6%) with L233-Tax disobeyed the log-normal distribution. These findings suggest that the animals affected by EBL were infected with the virus at a particular point in life, probably less than a few months after birth. Median age of those with P233-Tax was 22 months older than that with L233-Tax and geometric means exhibited a significant difference (P<0.01). It is also quite unlikely that viruses carrying the particular Tax protein infect older cattle. Here, we conclude that BLV could be divided into two categories on the basis of amino acid at position 233 of the Tax protein, which strongly correlated with leukemogenicity.
authors.affiliation: Laboratory of Microbiology and Immunology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Inoue
authors.forename: Keiko
authors.initials: K
authors.lastname: Matsumura
authors.forename: Norihiko
authors.initials: N
authors.lastname: Soma
authors.forename: Shintaro
authors.initials: S
authors.lastname: Hirasawa
authors.forename: Mayuko
authors.initials: M
authors.lastname: Wakimoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Arakaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Osawa
authors.forename: Katsunori
authors.initials: K
authors.lastname: Okazaki
mesh_terms: D017677:Age Distribution; D000483:Alleles; D000818:Animals; D002417:Cattle; D016583:Enzootic Bovine Leukosis / Q000821:virology*; D005260:Female; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000235:genetics*; D014644:Genetic Variation; D007564:Japan; D001909:Leukemia Virus, Bovine / Q000235:genetics* / Q000472:pathogenicity*; D009154:Mutation / Q000235:genetics*; D010802:Phylogeny; D016133:Polymerase Chain Reaction
chemical_list: D016356:Gene Products, tax
keywords: Bovine leukemia virus; Enzootic bovine leucosis; Leukemogenicity; Mutation; Tax protein