{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T22:11:18Z","timestamp":1753740678878,"version":"3.37.3"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"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\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001323","name":"Poliomyelitis Research Foundation","doi-asserted-by":"publisher","award":["# 16\/67"],"award-info":[{"award-number":["# 16\/67"]}],"id":[{"id":"10.13039\/501100001323","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of KwaZulu-Natal\u2019s College of Health Sciences"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Commonly, protease inhibitor failure is characterized by the development of multiple protease resistance mutations (PRMs). While the impact of PRMs on therapy failure are understood, the introduction of Gag mutations with protease remains largely unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Here, we utilized phylogenetic analyses and Bayesian network learning as tools to understand Gag-protease coevolution and elucidate the pathways leading to Lopinavir failure in HIV-1 subtype C infected patients. Our analyses indicate that while PRMs coevolve in response to drug selection pressure within protease, the Gag mutations added to the existing network while specifically interacting with known Lopinavir failure PRMs. Additionally, the selection of mutations at specific positions in Gag-protease suggests that these coevolving mutational changes occurs to maintain structural integrity during Gag cleavage.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btz076","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T13:15:11Z","timestamp":1549977311000},"page":"3219-3223","source":"Crossref","is-referenced-by-count":8,"title":["Gag-protease coevolution shapes the outcome of lopinavir-inclusive treatment regimens in chronically infected HIV-1 subtype C patients"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5010-5076","authenticated-orcid":false,"given":"V","family":"Marie","sequence":"first","affiliation":[{"name":"KwaZulu-Natal Research Innovation and Sequencing Platform, University of KwaZulu-Natal , Durban, South Africa"}]},{"given":"M","family":"Gordon","sequence":"additional","affiliation":[{"name":"KwaZulu-Natal Research Innovation and Sequencing Platform, University of KwaZulu-Natal , Durban, South Africa"}]}],"member":"286","published-online":{"date-parts":[[2019,2,12]]},"reference":[{"key":"2023013108003224500_btz076-B1","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.3390\/v2112509","article-title":"Molecular basis for drug resistance in HIV-1 protease","volume":"2","author":"Ali","year":"2010","journal-title":"Viruses"},{"key":"2023013108003224500_btz076-B2","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1093\/jac\/dkr569","article-title":"Frequency and patterns of protease gene resistance mutations in HIV-infected patients treated with lopinavir\/ritonavir as their first protease inhibitor","volume":"67","author":"Barber","year":"2012","journal-title":"J. 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