Abstract
BackgroundThe randomness of retroviral integration has been debated for many years. Recent evidence indicates that integration site selection is not random, and that it is influenced by both viral and cellular factors. To study the role of DNA structure in site selection, retroviral integration near matrix attachment regions (MARs) was analyzed for three different groups of retroviruses. The objective was to assess whether integration near MARs may be a factor for integration site selection.ResultsResults indicated that MLV, SL3-3 MuLV, HIV-1 and HTLV-1 integrate preferentially near MARs, specifically within 2-kilobases (kb). In addition, a preferential position and orientation relative to the adjacent MAR was observed for each virus. Further analysis of SL3-3 MuLV insertions in common integration sites (CISs) demonstrated a higher frequency of integration near MARs and an orientation preference that was not observed for integrations outside CISs.ConclusionThese findings contribute to a growing body of evidence indicating that retroviral integration is not random, that MARs influence integration site selection for some retroviruses, and that integration near MARs may have a role in the insertional activation of oncogenes by gammaretroviruses.
Highlights
The randomness of retroviral integration has been debated for many years
This method has been validated to predict the presence of matrix attachment regions (MARs) accurately, recent evidence indicates that stress-induced destabilization of duplex DNA is not sufficient for a sequence to bind to the nuclear matrix; the use of stressinduced duplex destabilization (SIDD) for the prediction of MARs may lead
The results indicated that gammaretroviruses (MLV and SL3-3), lentivirus (HIV-1) and deltaretrovirus (HTLV-1) integrate preferentially near MARs, within 2-kb (Figure 2)
Summary
The randomness of retroviral integration has been debated for many years. To study the role of DNA structure in site selection, retroviral integration near matrix attachment regions (MARs) was analyzed for three different groups of retroviruses. The degree of randomness of proviral integration has been debated for many years [1,2]. Before the completion and publication of the human and mouse genome databases, theories for randomness of retroviral integration were difficult to prove or disprove because of the technical challenge of analyzing a large sample size of integrations from infected cells. Since publication of the genome databases, several studies have isolated and mapped hundreds of proviral insertion sites for murine leukemia virus (page number not for citation purposes)
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