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A Mos1 transposase in vivo assay to screen new HIV-1 integrase inhibitors
The integrase and transposase enzymes of retrovirus and transposons, respectively, share the catalytic DDE domain. In vitro assays showed that inhibitors of HIV-1 integrase generally inhibit the mariner Mos1 transposase. Using a Drosophila strain in which the mobilisation of the mariner element can...
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Published in: | Genetica 2018-04, Vol.146 (2), p.243-247 |
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Main Authors: | , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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Summary: | The integrase and transposase enzymes of retrovirus and transposons, respectively, share the catalytic DDE domain. In vitro assays showed that inhibitors of HIV-1 integrase generally inhibit the
mariner
Mos1 transposase. Using a
Drosophila
strain in which the mobilisation of the
mariner
element can be quantified by mosaic eyes, we showed that flies maintained in medium containing 210 µM to 4 mM of raltegravir, or 1 or 2 mM of dolutegravir, which are HIV-1 integrase inhibitor used in AIDS treatment, have 23–33% less somatic mobilisation in mosaic eyes when treated with raltegravir and 28–32% when treated with dolutegravir. The gene expression of the
mariner
transposase gene, estimated by qPCR, is similar among treated and control flies. The results suggest that in vivo assays using
Drosophila
can be used as a primary screening of inhibitory drugs for transposase and retroviral integrase. The advantages of this assay are that it is easy, quick, cheap and is an in vivo test, meaning that the tested substance has to have been taken in by cells and has arrived at the target site, which is not the case when in vitro assays are applied. |
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ISSN: | 0016-6707 1573-6857 |
DOI: | 10.1007/s10709-018-0007-1 |