Bovine leukemia virus transmembrane protein gp30 physically associates with the down-regulatory phosphatase SHP-1

In B lymphocytes, the down-regulatory phosphatase SHP-1 associates with CD2 2 and CD32b (also known as Fc gamma RIIB) and acts as a critical negative r egulator of B-cell receptor signaling. Bovine leukemia virus, a retrovirus of the HTLV/BLV group, causes persistently increased numbers of peripheral blood B lymphocytes, known as persistent lymphocytosis (FL) and, in some an imals, progression to B-cell leukemia and/or lymphoma. Here, we show that S HP-1 associates with the bovine leukemia virus transmembrane protein, gp30. This interaction is either direct or indirect. The inter-action is depende nt on tyrosine phosphorylation, and the interaction increases after cell st imulation with sodium pervanadate. The gp30-SHP-1 interaction is seen in al l of the BLV-infected, FL animals tested, but is not seen in uninfected ani mals or in most BLV-infected, non-FL animals, which do not express signific ant quantities of gp30. However, one BLV-infected, non-FL animal expressed large quantities of gp30, yet no gp30-SHP-1 interaction was detected, sugge sting that there may Be other factors in cells from the FL animals that fac ilitate the gp30-SHP-1 interaction. The association of gp30 and SHP-1 sugge sts the hypothesis that gp30 may act as a decoy to sequester SHP-1, resulti ng in up-regulation of B-cell receptor signaling. The implication of this c ould be a novel mechanism of viral activation of lymphocytes by removal of a down-regulatory phosphatase. (C) 1999 Academic Press.