{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:50:44Z","timestamp":1791175844937,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,2,6]],"date-time":"2013-02-06T00:00:00Z","timestamp":1360108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo a Pesquisa do Estado de S\u00e3o Paulo","award":["2009\/14277-9-2010\/19054-5"],"award-info":[{"award-number":["2009\/14277-9-2010\/19054-5"]}]},{"name":"Capes\/Escola de Altos Estudos"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Several new direct\u2010acting antiviral (<jats:styled-content style=\"fixed-case\">DAA<\/jats:styled-content>) drugs are in development for chronic hepatitis C viral (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>) infection, and <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>3\u2010<jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>4A serine protease and the <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>5B <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010dependent <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> polymerase have been the major targets. <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> variants displaying drug\u2010resistant phenotypes have been observed both <jats:italic>in vitro<\/jats:italic> and during clinical trials. Our aim was to characterize amino acid changes at positions previously associated with resistance in protease (<jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>3) and polymerase (<jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>5B) regions from treatment\u2010na\u00efve <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> patients infected with genotypes 1a, 1b and 3a. All 1383 <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>3 protease sequences (genotype 1a\u00a0=\u00a0680, 1b\u00a0=\u00a0498 and 3a\u00a0=\u00a0205) and 806 <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>5B polymerase sequences (genotypes 1a\u00a0=\u00a0471, 1b\u00a0=\u00a0329, 3a\u00a0=\u00a06) were collected from <jats:italic>Los Alamos<\/jats:italic> databank. Genotype 3a protease sequences showed the typical low\u2010level resistance mutation V36L. <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>3 sequences from other genotypes presented mutations on positions 36, 39, 41, 43, 54, 80, 109, 155 and 168 in a frequency lower than 2%, except for the mutation Q80R found in 35% of genotype 1a isolates. Polymerase sequences from genotype 3a patients showed five typical mutations: L419I, I424V, I482L, V499A and S556G. Two positions presented high polymorphism in the <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>5B region from genotype 1a (V499A) and genotype 1b (C316N) subjects. Our results demonstrated a natural profile of genotype 3a that can be associated with the pre\u2010existence of <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> variants resistant to first\u2010generation protease inhibitors and to non\u2010nucleoside polymerase inhibitors. Likewise, genotype 1b isolates and genotype 1a sequences exhibited pre\u2010existing mutations associated with resistance to Palm <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> and Thumb I polymerase inhibitors, respectively.<\/jats:p>","DOI":"10.1111\/jvh.12051","type":"journal-article","created":{"date-parts":[[2013,2,6]],"date-time":"2013-02-06T08:59:59Z","timestamp":1360141199000},"page":"414-421","source":"Crossref","is-referenced-by-count":42,"title":["The presence of resistance mutations to protease and polymerase inhibitors in <scp>H<\/scp>epatitis <scp>C<\/scp> virus sequences from the <i><scp>L<\/scp>os <scp>A<\/scp>lamos<\/i> databank"],"prefix":"10.1111","volume":"20","author":[{"given":"R.","family":"Alves","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Hepatologia Molecular Aplicada Setor de Hepatites Divis\u00e3o de Gastroenterologia Universidade Federal de S\u00e3o Paulo Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. T. L.","family":"Queiroz","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunoparasitologia CPqGM \u2013 FIOCRUZ Salvador Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. G.","family":"Pessoa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology University of Sao Paulo School of Medicine Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. F.","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology University of Sao Paulo School of Medicine Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. F. C.","family":"Mazo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology University of Sao Paulo School of Medicine Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. J.","family":"Carrilho","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology University of Sao Paulo School of Medicine Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. J.","family":"Carvalho\u2010Filho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Hepatologia Molecular Aplicada Setor de Hepatites Divis\u00e3o de Gastroenterologia Universidade Federal de S\u00e3o Paulo Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. M. V. G.","family":"de Carvalho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Hepatologia Molecular Aplicada Setor de Hepatites Divis\u00e3o de Gastroenterologia Universidade Federal de S\u00e3o Paulo Sao Paulo Brazil"},{"name":"Imunologia Viral Instituto Butantan Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,2,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2010.03432.x"},{"issue":"4","key":"e_1_2_8_3_1","first-page":"132","article-title":"Moving beyond interferon alfa: investigational drugs for hepatitis C virus infection","volume":"18","author":"Wyles DL","year":"2010","journal-title":"Top HIV Med"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-140-5-200403020-00010"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06102-5"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020047"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2010.03430.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/apc.2007.0199"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01452-09"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1013086"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1010494"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009482"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1012912"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.211417"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.07.013"},{"issue":"12","key":"e_1_2_8_16_1","first-page":"938","article-title":"Filibuvir, a non\u2010nucleoside NS5B polymerase inhibitor for the potential oral treatment of chronic HCV infection","volume":"13","author":"Beaulieu PL","year":"2010","journal-title":"IDrugs"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61384-0"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24788"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.35.1.201-207.1997"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22673"},{"issue":"4","key":"e_1_2_8_21_1","first-page":"10","article-title":"Response rates to standard interferon treatment in HCV genotype 3a","volume":"21","author":"Qureshi S","year":"2009","journal-title":"J Ayub Med Coll Abbottabad"},{"issue":"5","key":"e_1_2_8_22_1","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1177\/135965350701200504","article-title":"Resistance profiling of hepatitis C virus protease inhibitors using full\u2010length NS3","volume":"12","author":"Dahl G","year":"2007","journal-title":"Antivir Ther"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01081-08"},{"issue":"7","key":"e_1_2_8_24_1","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1177\/135965350601100702","article-title":"Resistance of hepatitis C virus to NS3\u20104A protease inhibitors: mechanisms of drug resistance induced by R155Q, A156T, D168A and D168V mutations","volume":"11","author":"Courcambeck J","year":"2006","journal-title":"Antivir Ther"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23192"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00863-07"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2010.500285"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2011.07.008"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002417"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20819"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm404"},{"key":"e_1_2_8_32_1","first-page":"4","article-title":"BioEdit: a user\u2010friendly biological sequence alignment editor and analysis program for Windows 95\/98\/NT","volume":"41","author":"Hall Ta","year":"1999","journal-title":"Nucleic Acids Symp"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msr121"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506462200"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-1-r16"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2007.10.006"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00556-10"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2011.01449.x"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.10146"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1089\/aid.1992.8.1549"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2007.11.010"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506407200"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.6.4.463"},{"issue":"4","key":"e_1_2_8_44_1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1177\/135965350801300413","article-title":"Mapping natural polymorphisms of hepatitis C virus NS3\/4A protease and antiviral resistance to inhibitors in worldwide isolates","volume":"13","author":"L\u00f3pez\u2010Labrador F","year":"2008","journal-title":"Antivir Ther"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039652"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2010.05.006"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2009.01125.x"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.14.7352-7359.2004"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.07.007"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.10.056"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01548-07"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00777-10"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.08.033"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.40.9.3127-3134.2002"}],"container-title":["Journal of Viral Hepatitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.12051","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.12051","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.12051","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T09:29:55Z","timestamp":1700645395000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvh.12051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,6]]},"references-count":53,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2013,6]]}},"alternative-id":["10.1111\/jvh.12051"],"URL":"https:\/\/doi.org\/10.1111\/jvh.12051","archive":["Portico"],"relation":{},"ISSN":["1352-0504","1365-2893"],"issn-type":[{"value":"1352-0504","type":"print"},{"value":"1365-2893","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,6]]}}}