GENES IN THE PX REGION OF HUMAN T-CELL LEUKEMIA-VIRUS-I INFLUENCE VAVPHOSPHORYLATION IN T-CELLS

Human T cell leukemia virus I (HTLV-I) causes acute leukemic disease i n a low percentage of infected individuals through obscure mechanisms. Our studies compare two rabbit HTLV-I-infected T cell lines: one, RH/ K34, causes lethal experimental leukemia and the other, RH/K30, mediat es asymptomatic infection. We show herein that the product of the prot ooncogene vav is constitutively Tyrphosphorylated in RH/K34 but not in RH/K30. A role for the retrovirus in phosphorylation of Vav was assig ned by transfection experiments with molecular clones of HTLV-I derive d from the two lines. The HTLV-I molecular clone from RH/K30, but not that from RH/K34, down-regulates Vav phosphorylation in a Herpesvirus ateles-transformed T cell line, Use of recombinant virus clones reveal ed that a pX region sequence differing by two nucleotides between the two clones mediates this down-regulation, Because Vav is involved in T cell signaling and Vav phosphorylation occurs upon activation of T ce lls, control of the activation state of Vav by viral proteins may rela te to the leukemogenic potential of certain HTLV-I-infected cells.