THE CREB, ATF-1, AND ATF-2 TRANSCRIPTION FACTORS FROM BOVINE LEUKEMIAVIRUS-INFECTED B-LYMPHOCYTES ACTIVATE VIRAL EXPRESSION

Efficient transcription and replication of the bovine leukemia virus ( BLV) genome require both the viral long terminal repeat (LTR) and the virus-coded transcriptional activator Tax, which functions through a 2 1-bp sequence (Tax-responsive element [TxRE]) which is repeated three times within the LTR, Since Tax: does not bind directly to DNA, host c ell transcription factors play a central role in BLV expression, Elect rophoretic mobility shift assays with nuclear extracts prepared with i nfected bovine B lymphocytes revealed five TxRE-specific complexes (C1 , C2, C3, C4, and C5). Here, by using a UV-induced indirect labeling t echnique (UV cross-linking) in conjunction with mobility shift assays, eight major polypeptides of 31, 33, 42, 46, 51, 57, 87, and 119 kDa w ere identified within these five complexes. Immunoprecipitation experi ments identified the 57- and 119-kDa proteins as cyclic AMP response e lement-binding (CREB) proteins, the 46- and 51-kDa proteins as activat ing transcription factor-1 (ATF-1), and the 87-kDa as protein ATF-2. A ll of these proteins (except the ATF-1 protein of 51 kDa) belong to th e complex C1, which is the major complex identified in freshly isolate d BLV-infected lymphocytes from cattle with persistent lymphocytosis. In transient-cotransfection experiments, these three transcription fac tors were able to activate LTR-directed gene expression in the presenc e of protein kinase A or Ca2+/calmodulin-dependent protein kinase IV. CREB protein, ATF-1, and ATF-2 thus appear to be the major transcripti on factors involved in the early stages of viral expression.