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, pol, and env genes that function through cis-acting sequences to replicate the RNA genome to the DNA provirus. Genetically more complex retroviruses also encode regulatory genes and cis-acting 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 to replicate the gag, pol, and env genes of the more complex bovine leukemia virus (BLV) in the absence of regulatory genes and cis-acting response sequences. Most of the cis-acting sequences involved in the replication and regulation of BLV were replaced by the cis-acting transcriptional control sequences of a simpler retrovirus, spleen necrosis virus. We found that the resulting hybrid BLV derivatives can replicate independently of BLV Tax and Rex and the Tax and Rex cis-acting response sequences, as measured by successive passages of virus on target cells, detection of provirus sequences, and analyses of provirus and encapsidated RNAs.