GENETICALLY SIMPLER BOVINE LEUKEMIA-VIRUS DERIVATIVES CAN REPLICATE INDEPENDENTLY OF TAX AND REX

Retrovirus genomes have a conserved modular organization that consists of trans-acting gag, pal, and env genes that function through cis-act ing sequences to replicate the RNA genome to the DNA provirus. Genetic ally more complex retroviruses also encode regulatory genes and cis-ac ting sequences that are essential for their replication. We sought to convert a more complex retrovirus into a simpler retrovirus derivative that can replicate. We constructed novel, hybrid retrovirus vectors t o replicate the gag, pol, and env genes of the more complex bovine leu kemia virus (BLV) in the absence of regulatory genes and cis-acting re sponse sequences. Most of the cis-acting sequences involved in the rep lication and regulation of BLV were replaced by the cis-acting transcr iptional control sequences of a simpler retrovirus, spleen necrosis vi rus. We found that the resulting hybrid BLV derivatives can replicate independently of BLV Tax and Rex and the Tax and Rex cis-acting respon se sequences, as measured by successive passages of virus on target ce lls, detection of provirus sequences, and analyses of provirus and enc apsidated RNAs.