Bovine leukemia virus integration site selection in cattle that develop leukemia

It is essential for efficient replication of retroviruses that the viral genome is integrated into the host genome after reverse transcription. Some retroviruses are preferentially integrated into certain genomic regions that may differ depending on the disease. In this study, we analyzed the integration site of bovine leukemia virus (BLV) in leukemic cells and 55 integration sites were determined. Although the integration sites were not located in a particular chromosome, the BLV provirus was integrated into transcription units at a frequency of 43.6% (24/55) and the transcriptional direction of the provirus was in accordance with that of the integrated host genes in 62.5% (15/24). The integration sites were located in introns of the host gene, excluding only one site, which was located in downstream from a stop codon. BLV provirus was never found in a protein coding sequence (CDS) in this study. Moreover, the BLV provirus did not favor integration near transcription start sites and CpG islands, or repetitive sequences such as transposons. Therefore, the possibility that the integration of the BLV provirus disrupts the host gene is very low. Although a hot spot was not found in the BLV provirus integration sites, the provirus favored the integration into regions disadvantageous for viral gene expression since no integration site was preferentially located into/near CDS, transcription start site or CpG island. It is suggested that the integration site of the BLV provirus in leukemic cells is related to the suppression of viral gene expression.