Host soluble factors that regulate the synthesis of the major core protein of the bovine leukemia virus (BLV) in a naturally infected neoplastic B-cell line.

Bovine leukemia virus (BLV) is a B-cell tropic Deltaretrovirus that induces a lifelong infection and causes a fatal lymphosarcoma in less than 10% of the infected cattle. BLV is usually present in its host in a transcriptional repressed state but becomes de-repressed a few hours after the infected lymphocytes are cultured in vitro. In the present study we have examined the effect of soluble host factors and various substances on the synthesis of the major BLV protein (p24) in a permanent culture (cell line NBC-10) of neoplastic B-lymphocytes derived from BLV-infected cattle. Certain batches of fetal calf serum (FCS) and bovine platelet lysates (PLy) induced a rapid and drastic increase of the synthesis of BLVp24 in the NBC-10 cells. Neutralization experiments with specific antibodies demonstrated that the transforming growth factor-beta (TGF-beta) was responsible for the stimulatory activity of FCS and PLy on the synthesis of BLVp24 in the NBC-10 cells. Recombinant TGF-beta also stimulated the synthesis of BLVp24 in cultures of peripheral blood mononuclear cells (PBMCs) obtained from BLV-infected cattle. Mitogens, phorbol-myristate-acetate and prostaglandin E(2), previously shown to stimulate the expression of BLV in cultures of PBMC, did not induce the synthesis of BLVp24 in cultures of NBC-10 cells. Plasma, serum and milk from BLV-negative cattle inhibited the synthesis of BLVp24 induced by FCS, PLy or TGF-beta in the NBC-10 cells. The blocking activity was found in the whey and the beta-casein fractions of bovine milk. The relevance of these findings with regard to the previously reported plasma factor (PBB) with blocking activity on the expression of BLV in short-term PBMC cultures is discussed. Based on the information obtained in the present study we have standardized a reproducible and rapid assay system for the identification of factors that regulate the synthesis of BLVp24 in naturally infected neoplastic B cells.