A paper on HTLV

Today, I read a paper about association of integration of HTLV-1 into transcriptionally active genomic regions with proviral expression and with HTLV-1 associated myelopathy/tropical spastic paraperesis (HAM/TSP). The paper is from the lab of Dr. Charles Bangham, Imperial College, London.
In this blog, I would like to give a brief introduction of the problem and the virus. HTLV-1 or human T lymphotrophic virus type 1 is a human RNA retrovirus that causes two types of diseases: HTLV-1 associated myelopathy/tropical spastic paraperesis (HAM/TSP), a chronic disabiling disease of the central nervous system and adult T cell leukaemia (ATL), a neoplastic disease. As with other retroviruses, the virus replicates by integrating into host cell genome. Studies are being carried out in different parts of the world on the integration of the virus and the distribution of integration sites on human genome. In this paper the hypothesis that invivo selection influences the distribution of proviral integration sites in persistent HTLV-1 infection was tested.
It has been shown that integration of virus into host genome occurs at specific target sites. It has also been observed that target site preferences of HTLV-1 are similar to another retrovirus, avian sarcoma leucosis virus (ASLV). Both targeted genes, transcriptional start sites and CpG islands. Since the integrases of HTLV-1 and ASLV are more similar to each other than to other retroviruses, this observation supports the hypothesis that integrases play a major role in determing integration site of the viruses.
There are many unanswered questions on HTLV- 1 infection. It has been shown that proviral load remains constant over time in a patient but it has been shown to vary among patients. The reason for this variation is not clear.
It was recently demonstrated that the difference in the efficiency of cytotoxic T cell response among individuals was resposible for 30% of the observed variation between individual in proviral load. It has also been demonstrated that the rate of proviral expression is resposible for an additional 13% variation in proviral load.
In this paper, the authors have postulated that the CTL independent variation in proviral load is due to molecular factors that affect proviral load and provirus expression and one such factor is integration site of the virus. Thus, in the present study the genomic characteristics of HTLV-1 integration sites resulting from infection in a cell culture system in vitro were compared with those of integration sites resulting from freshly isolated PBMCs from patients with HTLV-1 chronic infection (in vivo).