{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T23:36:41Z","timestamp":1783121801196,"version":"3.54.6"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T00:00:00Z","timestamp":1639180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI146017 to S.G.S. and A.H."],"award-info":[{"award-number":["R01 AI146017 to S.G.S. and A.H."]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nahmias-Schinazi Distinguished Chair in Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>In vitro selection experiments identified viruses resistant to integrase strand transfer inhibitors (INSTIs) carrying mutations in the G-tract (six guanosines) of the 3\u2032-polypurine tract (3\u2032-PPT). A clinical study also reported that mutations in the 3\u2032-PPT were observed in a patient receiving dolutegravir monotherapy. However, recombinant viruses with the 3\u2032-PPT mutations that were found in the clinical study were recently shown to be susceptible to INSTIs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To identify the specific mutation(s) in the G-tract of the 3\u2032-PPT for acquiring INSTI resistance, we constructed infectious clones bearing single or multiple mutations and systematically characterized the susceptibility of these clones to both first- and second-generation INSTIs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The infectious clones were tested for their infectivity and susceptibility to INSTIs in a single-cycle assay using TZM-bl cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A single mutation of thymidine (T) at the fifth position (GGG GTG) in the G-tract of the 3\u2032-PPT had no effect on INSTI resistance. A double mutation, cytidine (C) or \u2018T\u2019 at the second position and \u2018T\u2019 at the fifth position (GCG GTG and GTG GTG), increased resistance to INSTIs, with the appearance of a plateau in the maximal percentage inhibition (MPI) of the dose\u2013response curves, consistent with a non-competitive mechanism of inhibition.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Mutations at the second and fifth positions in the G-tract of the 3\u2032-PPT may result in complex resistance mechanism(s), rather than simply affecting INSTI binding at the IN active site.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkab448","type":"journal-article","created":{"date-parts":[[2021,12,4]],"date-time":"2021-12-04T12:07:51Z","timestamp":1638619671000},"page":"574-577","source":"Crossref","is-referenced-by-count":14,"title":["Specific mutations in the HIV-1 G-tract of the 3\u2032-polypurine tract cause resistance to integrase strand transfer inhibitors"],"prefix":"10.1093","volume":"77","author":[{"given":"Atsuko","family":"Hachiya","sequence":"first","affiliation":[{"name":"Clinical Research Center, National Hospital Organization Nagoya Medical Center, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Kubota","sequence":"additional","affiliation":[{"name":"Clinical Research Center, National Hospital Organization Nagoya Medical Center, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urara","family":"Shigemi","sequence":"additional","affiliation":[{"name":"Clinical Research Center, National Hospital Organization Nagoya Medical Center, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Ode","sequence":"additional","affiliation":[{"name":"Clinical Research Center, National Hospital Organization Nagoya Medical Center, Aichi, 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasumasa","family":"Iwatani","sequence":"additional","affiliation":[{"name":"Clinical Research Center, National Hospital Organization Nagoya Medical Center, Aichi, Japan"},{"name":"Department of AIDS Research, Nagoya University Graduate School of Medicine, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,12,11]]},"reference":[{"key":"2022022312584618900_dkab448-B1","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1128\/AAC.01209-10","article-title":"In vitro antiretroviral properties of S\/GSK1349572, a next-generation HIV integrase inhibitor","volume":"55","author":"Kobayashi","year":"2011","journal-title":"Antimicrob Agents Chemother"},{"key":"2022022312584618900_dkab448-B2","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1128\/AAC.04844-14","article-title":"Effects of raltegravir or elvitegravir resistance signature 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