{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:21:01Z","timestamp":1791328861232,"version":"4.3.1"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2009,3,20]],"date-time":"2009-03-20T00:00:00Z","timestamp":1237507200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1000345","type":"journal-article","created":{"date-parts":[[2009,3,19]],"date-time":"2009-03-19T18:29:10Z","timestamp":1237487350000},"page":"e1000345","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":128,"title":["Gag Mutations Strongly Contribute to HIV-1 Resistance to Protease Inhibitors in Highly Drug-Experienced Patients besides Compensating for Fitness Loss"],"prefix":"10.1371","volume":"5","author":[{"given":"Elisabeth","family":"Dam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romina","family":"Quercia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e4rbel","family":"Glass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Descamps","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile","family":"Launay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Duval","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Georg","family":"Kr\u00e4usslich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan J.","family":"Hance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Clavel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"ANRS 109 Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2009,3,20]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/374569a0","article-title":"In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors.","volume":"374","author":"JH Condra","year":"1995","journal-title":"Nature"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/nm0796-760","article-title":"Ordered accumulation of mutations in HIV protease confers resistance to ritonavir.","volume":"2","author":"A Molla","year":"1996","journal-title":"Nat Med"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"8524","DOI":"10.1128\/JVI.74.18.8524-8531.2000","article-title":"Retracing the evolutionary pathways of human immunodeficiency virus type 1 resistance to protease inhibitors: virus fitness in the absence and in the presence of drug.","volume":"74","author":"F Mammano","year":"2000","journal-title":"J Virol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"11104","DOI":"10.1128\/JVI.76.21.11104-11112.2002","article-title":"Evolution of phenotypic drug susceptibility and viral replication capacity during long-term virologic failure of protease inhibitor therapy in human immunodeficiency virus-infected adults.","volume":"76","author":"JD Barbour","year":"2002","journal-title":"J Virol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1056\/NEJMra025195","article-title":"HIV drug resistance.","volume":"350","author":"F Clavel","year":"2004","journal-title":"N Engl J Med"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1099\/0022-1317-77-3-419","article-title":"Resistance of human immunodeficiency virus type 1 to protease inhibitors: selection of resistance mutations in the presence and absence of the drug.","volume":"77 (Pt 3)","author":"AM Borman","year":"1996","journal-title":"J Gen Virol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"3763","DOI":"10.1128\/JVI.70.6.3763-3769.1996","article-title":"Second locus involved in human immunodeficiency virus type 1 resistance to protease inhibitors.","volume":"70","author":"L Doyon","year":"1996","journal-title":"J Virol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"7632","DOI":"10.1128\/JVI.72.9.7632-7637.1998","article-title":"Resistance-associated loss of viral fitness in human immunodeficiency virus type 1: phenotypic analysis of protease and gag coevolution in protease inhibitor-treated patients.","volume":"72","author":"F Mammano","year":"1998","journal-title":"J Virol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"6662","DOI":"10.1128\/JVI.71.9.6662-6670.1997","article-title":"Drug resistance during indinavir therapy is caused by mutations in the protease gene and in its Gag substrate cleavage sites.","volume":"71","author":"YM Zhang","year":"1997","journal-title":"J Virol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1128\/JVI.75.2.589-594.2001","article-title":"Human immunodeficiency virus type 1 protease cleavage site mutations associated with protease inhibitor cross-resistance selected by indinavir, ritonavir, and\/or saquinavir.","volume":"75","author":"HC Cote","year":"2001","journal-title":"J Virol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.virol.2005.11.049","article-title":"Co-evolution of nelfinavir-resistant HIV-1 protease and the p1-p6 substrate.","volume":"347","author":"M Kolli","year":"2006","journal-title":"Virology"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"7398","DOI":"10.1128\/JVI.76.15.7398-7406.2002","article-title":"Changes in human immunodeficiency virus type 1 Gag at positions L449 and P453 are linked to I50V protease mutants in vivo and cause reduction of sensitivity to amprenavir and improved viral fitness in vitro.","volume":"76","author":"MF Maguire","year":"2002","journal-title":"J Virol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1371\/journal.pmed.0040036","article-title":"A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism.","volume":"4","author":"M Nijhuis","year":"2007","journal-title":"PLoS Med"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1089\/088922200414992","article-title":"HIV type 1 protease cleavage site mutations and viral fitness: implications for drug susceptibility phenotyping assays.","volume":"16","author":"LH Robinson","year":"2000","journal-title":"AIDS Res Hum Retroviruses"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.virol.2008.05.029","article-title":"Drug-associated changes in amino acid residues in Gag p2, p7(NC), and p6(Gag)\/p6(Pol) in human immunodeficiency virus type 1 (HIV-1) display a dominant effect on replicative fitness and drug response.","volume":"378","author":"SK Ho","year":"2008","journal-title":"Virology"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1089\/08892220050116970","article-title":"Polymorphism of HIV type 1 gag p7\/p1 and p1\/p6 cleavage sites: clinical significance and implications for resistance to protease inhibitors.","volume":"16","author":"F Bally","year":"2000","journal-title":"AIDS Res Hum Retroviruses"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1006\/viro.1996.0266","article-title":"Natural variation in HIV-1 protease, Gag p7 and p6, and protease cleavage sites within gag\/pol polyproteins: amino acid substitutions in the absence of protease inhibitors in mothers and children infected by human immunodeficiency virus type 1.","volume":"219","author":"KA Barrie","year":"1996","journal-title":"Virology"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"5952","DOI":"10.1074\/jbc.M108005200","article-title":"Amino acid substitutions in Gag protein at non-cleavage sites are indispensable for the development of a high multitude of HIV-1 resistance against protease inhibitors.","volume":"277","author":"H Gatanaga","year":"2002","journal-title":"J Biol Chem"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1128\/AAC.48.2.444-452.2004","article-title":"Gag non-cleavage site mutations contribute to full recovery of viral fitness in protease inhibitor-resistant human immunodeficiency virus type 1.","volume":"48","author":"L Myint","year":"2004","journal-title":"Antimicrob Agents Chemother"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.antiviral.2006.01.004","article-title":"Cooperative contribution of gag substitutions to nelfinavir-dependent enhancement of precursor cleavage and replication of human immunodeficiency virus type-1.","volume":"70","author":"S Matsuoka-Aizawa","year":"2006","journal-title":"Antiviral Res"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"10047","DOI":"10.1128\/JVI.02496-06","article-title":"Mutational analysis of the C-terminal gag cleavage sites in human immunodeficiency virus type 1.","volume":"81","author":"LV Coren","year":"2007","journal-title":"J Virol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1177\/135965350601100708","article-title":"Compensatory mutations at the HIV cleavage sites p7\/p1 and p1\/p6-gag in therapy-naive and therapy-experienced patients.","volume":"11","author":"J Verheyen","year":"2006","journal-title":"Antivir Ther"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"12446","DOI":"10.1128\/JVI.78.22.12446-12454.2004","article-title":"Structural basis for coevolution of a human immunodeficiency virus type 1 nucleocapsid-p1 cleavage site with a V82A drug-resistant mutation in viral protease.","volume":"78","author":"M Prabu-Jeyabalan","year":"2004","journal-title":"J Virol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/0006-291X(89)90008-9","article-title":"Peptide substrates and inhibitors of the HIV-1 protease.","volume":"159","author":"ML Moore","year":"1989","journal-title":"Biochem Biophys Res Commun"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/nsmb785","article-title":"The stoichiometry of Gag protein in HIV-1.","volume":"11","author":"JA Briggs","year":"2004","journal-title":"Nat Struct Mol Biol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1093\/nar\/gkj458","article-title":"Nucleic acid binding and chaperone properties of HIV-1 Gag and nucleocapsid proteins.","volume":"34","author":"M Cruceanu","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1006\/jmbi.1994.1542","article-title":"HIV-1 reverse transcription. A termination step at the center of the genome.","volume":"241","author":"P Charneau","year":"1994","journal-title":"J Mol Biol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"3300","DOI":"10.1128\/JVI.72.4.3300-3306.1998","article-title":"Loss of viral fitness associated with multiple Gag and Gag-Pol processing defects in human immunodeficiency virus type 1 variants selected for resistance to protease inhibitors in vivo.","volume":"72","author":"V Zennou","year":"1998","journal-title":"J Virol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1097\/00002030-199910220-00008","article-title":"Analysis of HIV cross-resistance to protease inhibitors using a rapid single-cycle recombinant virus assay for patients failing on combination therapies.","volume":"13","author":"E Race","year":"1999","journal-title":"Aids"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1177\/135965350601100703","article-title":"Lamivudine and indinavir\/ritonavir maintenance therapy in highly pretreated HIV-infected patients (Vista ANRS 109).","volume":"11","author":"O Launay","year":"2006","journal-title":"Antivir Ther"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/0003-2697(87)90587-2","article-title":"Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa.","volume":"166","author":"H Schagger","year":"1987","journal-title":"Anal Biochem"}],"container-title":["PLoS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.ppat.1000345","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T10:45:29Z","timestamp":1684925129000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1000345"}},"subtitle":[],"editor":[{"given":"Jeremy","family":"Luban","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2009,3,20]]},"references-count":31,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2009,3,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1000345","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,3,20]]}}}