HTLV-1 Integration into Transcriptionally Active Genomic Regions Is Associated with Proviral Expression and with HAM/TSP
Figure 1
Integration of HTLV-1 in transcriptionally active genomic regions.
Panel A: Near gene transcriptional start sites and CpG islands. HTLV-1 showed significantly greater than expected frequency of integration in the vicinity of RefSeq transcriptional start sites (TxStart sites) and CpG islands in cell culture in vitro and in persistent infection in vivo. The vertical axes for the in vitro and in vivo datasets show the proportion of observed HTLV-1 integration sites or expected MRC sites in the vicinity of the respective genomic feature. * indicates a significant difference between HTLV-1 sites and MRCs, by χ-squared analysis (p<0.05). There was a significantly greater association with integration in the proximity of TxStart sites and CpG islands comparing the distribution of observed HTLV-1 integration sites to expected MRC sites in vivo and in vitro (vertical axis, in vitro vs in vivo). $ indicates a significant difference between the frequency of HTLV-1 in vivo sites and in vitro sites, by logistic regression (p<0.005). Panel B: In regions of high gene density. HTLV-1 showed an increased frequency of integration in gene dense regions. Gene density in regions from 25 kb to 1 Mb around the integration site was analysed. In all region sizes, there was a greater association of HTLV-1 integration in gene dense regions both in vivo and in vitro. However, there was a significantly greater association between proviral integration frequency and gene density in persistent infection in vivo than was seen in vitro. A graphical illustration of the 25 kb region and data on the logistic regression results comparing the in vivo and in vitro HTLV-1 datasets for the first three region sizes is given (Panel B).