{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:51:40Z","timestamp":1787003500475,"version":"build-2736575974"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,10,25]],"date-time":"2017-10-25T00:00:00Z","timestamp":1508889600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,10,25]],"date-time":"2017-10-25T00:00:00Z","timestamp":1508889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    FDA-approved integrase strand transfer inhibitors (raltegravir, elvitegravir and dolutegravir) efficiently inhibit HIV-1 replication. Here, we present fluorescence properties of these inhibitors. Dolutegravir displays an excitation mode particularly dependent on Mg\n                    <jats:sup>2+<\/jats:sup>\n                    chelation, allowing to directly probe its Mg\n                    <jats:sup>2+<\/jats:sup>\n                    -dependent binding to the prototype foamy virus (PFV) integrase. Dolutegravir-binding studied by both its fluorescence anisotropy and subsequent emission enhancement, strictly requires a preformed integrase\/DNA complex, the ten terminal base pairs from the 3\u2032-end of the DNA reactive strand being crucial to optimize dolutegravir-binding in the context of the ternary complex. From the protein side, mutation of any catalytic residue fully abolishes dolutegravir-binding. We also compared dolutegravir-binding to PFV F190Y, G187R and S217K mutants, corresponding to HIV-1 F121Y, G118R and G140S\/Q148K mutations that confer low-to-high resistance levels against raltegravir\/dolutegravir. The dolutegravir-binding properties derived from fluorescence-based binding assays and drug susceptibilities in terms of catalytic activity, are well correlated. Indeed, dolutegravir-binding to wild-type and F190Y integrases are comparable while strongly compromised with G187R and S217K. Accordingly, the two latter mutants are highly resistant to dolutegravir while F190Y shows only moderate or no resistance. Intrinsic fluorescence properties of dolutegravir are thus particularly suitable for a thorough characterization of both DNA-binding properties of integrase and resistance mutations.\n                  <\/jats:p>","DOI":"10.1038\/s41598-017-14564-w","type":"journal-article","created":{"date-parts":[[2017,10,19]],"date-time":"2017-10-19T07:34:50Z","timestamp":1508398490000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence"],"prefix":"10.1038","volume":"7","author":[{"given":"Elo\u00efse","family":"Thierry","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Lebourgeois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Delelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Deprez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,10,25]]},"reference":[{"key":"14564_CR1","doi-asserted-by":"publisher","first-page":"12730","DOI":"10.1021\/acs.chemrev.6b00125","volume":"116","author":"P Lesbats","year":"2016","unstructured":"Lesbats, P., Engelman, A. N. & Cherepanov, P. Retroviral DNA Integration. Chem. Rev. \n                           116, 12730\u201312757 (2016).","journal-title":"Chem. Rev."},{"key":"14564_CR2","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/nrmicro.2016.162","volume":"15","author":"M Lusic","year":"2017","unstructured":"Lusic, M. & Siliciano, R. F. Nuclear landscape of HIV-1 infection and integration. Nat. Rev. Microbiol. \n                           15, 69\u201382 (2017).","journal-title":"Nat. Rev. Microbiol."},{"key":"14564_CR3","doi-asserted-by":"crossref","unstructured":"Neamati, N. HIV-1 integrase: Mechanism and inhibitor design, Wiley series on drug discovery and development, Wiley & Sons: New York (2011).","DOI":"10.1002\/9781118015377"},{"key":"14564_CR4","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/nrmicro2747","volume":"10","author":"A Engelman","year":"2012","unstructured":"Engelman, A. & Cherepanov, P. 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HIV-1 integrase binds the viral RNA genome and is essential during virion morphogenesis. Cell \n                           166, 1257\u20131268 (2016).","journal-title":"Cell"},{"key":"14564_CR12","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-10-144","volume":"10","author":"E Le Rouzic","year":"2013","unstructured":"Le Rouzic, E. et al. Dual inhibition of HIV-1 replication by integrase-LEDGF allosteric inhibitors is predominant at the post-integration stage. Retrovirology \n                           10, 144 (2013).","journal-title":"Retrovirology"},{"key":"14564_CR13","doi-asserted-by":"publisher","first-page":"23569","DOI":"10.1074\/jbc.M116.753384","volume":"291","author":"D Patel","year":"2016","unstructured":"Patel, D. et al. A new class of allosteric HIV-1 Integrase inhibitors identified by crystallographic fragment screening of the catalytic core domain. J. Biol. Chem. \n                           291, 23569\u201323577 (2016).","journal-title":"J. Biol. 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