{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T23:47:04Z","timestamp":1762300024483,"version":"3.37.3"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,3,26]],"date-time":"2022-03-26T00:00:00Z","timestamp":1648252800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,26]],"date-time":"2022-03-26T00:00:00Z","timestamp":1648252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003339","name":"Spanish National Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003339","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["CD20\/00025","PI 13\/02269, PI17\/00164, PI16\/0684, PI19\/01127","PI 13\/02269, PI17\/00164, PI16\/0684, PI19\/01127","PI 13\/02269, PI17\/00164, PI16\/0684, PI19\/01127","PI 13\/02269, PI17\/00164, PI16\/0684, PI19\/01127","PI17\/00164","PI 13\/02269, PI17\/00164, PI16\/0684, PI19\/01127"],"award-info":[{"award-number":["CD20\/00025","PI 13\/02269, PI17\/00164, PI16\/0684, PI19\/01127","PI 13\/02269, PI17\/00164, PI16\/0684, PI19\/01127","PI 13\/02269, PI17\/00164, PI16\/0684, PI19\/01127","PI 13\/02269, PI17\/00164, PI16\/0684, PI19\/01127","PI17\/00164","PI 13\/02269, PI17\/00164, PI16\/0684, PI19\/01127"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Spanish Government","award":["RYC-2015-18241 and PID2019-107931GA-I00"],"award-info":[{"award-number":["RYC-2015-18241 and PID2019-107931GA-I00"]}]},{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"crossref","award":["ED431F 2018\/08"],"award-info":[{"award-number":["ED431F 2018\/08"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["SAF 2016-77894-R","SAF 2016-77894-R","SAF 2016-77894-R","SAF 2016-77894-R","SAF 2016-77894-R"],"award-info":[{"award-number":["SAF 2016-77894-R","SAF 2016-77894-R","SAF 2016-77894-R","SAF 2016-77894-R","SAF 2016-77894-R"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"name":"RIS-RETIC","award":["RD12\/0017\/0028, RD16\/0025\/0020 and RD16CIII\/0002\/0005","RD12\/0017\/0028, RD16\/0025\/0020 and RD16CIII\/0002\/0005"],"award-info":[{"award-number":["RD12\/0017\/0028, RD16\/0025\/0020 and RD16CIII\/0002\/0005","RD12\/0017\/0028, RD16\/0025\/0020 and RD16CIII\/0002\/0005"]}]},{"name":"ISCIII RETIC","award":["RD16\/0025\/0041"],"award-info":[{"award-number":["RD16\/0025\/0041"]}]},{"name":"Catalan Government and the European Social Fund","award":["AGAUR-FI_B 00582"],"award-info":[{"award-number":["AGAUR-FI_B 00582"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Retrovirology"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Long-Term Non-Progressors (LTNPs) are untreated Human Immunodeficiency virus type 1 (HIV-1) infected individuals able to control disease progression for prolonged periods. However, the LTNPs status is temporary, as viral load increases followed by decreases in CD4\u2009+\u2009T-cell counts. Control of HIV-1 infection in LTNPs viremic controllers, have been associated with effective immunodominant HIV-1 Gag-CD8\u2009+\u2009T-cell responses restricted by protective HLA-B alleles. Individuals carrying HLA-B*14:02 control HIV-1 infection is related to an immunodominant Env-CD8\u2009+\u2009T-cell response. Limited data are available on the contribution of HLA-B*14:02 CD8\u2009+\u2009T -cells in LTNPs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In this study, we performed a virological and immunological detailed analysis of an HLA-B*14:02 LNTP individual that lost viral control (LVC) 27\u00a0years after HIV-1 diagnosis. We analysed viral evolution and immune escape in HLA-B*14:02 restricted CD8\u2009+\u2009T -cell epitopes and identified viral evolution at the Env-EL9 epitope selecting the L592R mutation. By IFN-\u03b3 ELISpot and immune phenotype, we characterized HLA- B*14:02 HIV-1 CD8\u2009+\u2009T cell responses targeting, Gag-DA9 and Env-EL9 epitopes before and after LVC. We observed an immunodominant response against the Env-EL9 epitope and a decreased of the CD8 T\u2009+\u2009cell response over time with LVC. Loss of Env-EL9 responses was concomitant with selecting K588R\u2009+\u2009L592R mutations at Env-EL9. Finally, we evaluated the impact of Env-EL9 escape mutations on HIV-1 infectivity and Env protein structure. The K588R\u2009+\u2009L592R escape variant was directly related to HIV-1 increase replicative capacity and stability of Env at the LVC.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These findings support the contribution of immunodominant Env-EL9 CD8\u2009+\u2009T-cell responses and the imposition of immune escape variants with higher replicative capacity associated with LVC in this LNTP. These data highlight the importance of Env-EL9 specific-CD8\u2009+\u2009T-cell responses restricted by the HLA-B*14:02 and brings new insights into understanding long-term HIV-1 control mediated by Env mediated CD8\u2009+\u2009T-cell responses.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12977-022-00591-7","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T04:32:10Z","timestamp":1648528330000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Immunoescape of HIV-1 in Env-EL9 CD8\u2009+\u2009T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control"],"prefix":"10.1186","volume":"19","author":[{"given":"Ana","family":"Moyano","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar","family":"Blanch-Lombarte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Tarancon-Diez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuria","family":"Pedre\u00f1o-Lopez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Arenas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Alvaro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Concepci\u00f3n","family":"Casado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Olivares","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar","family":"Vera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"del Romero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilio","family":"L\u00f3pez-Gal\u00edndez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ezequiel","family":"Ruiz-Mateos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia G.","family":"Prado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Pernas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,3,26]]},"reference":[{"issue":"6","key":"591_CR1","doi-asserted-by":"crossref","first-page":"e11079","DOI":"10.1371\/journal.pone.0011079","volume":"5","author":"C Casado","year":"2010","unstructured":"Casado C, Colombo S, Rauch A, Martinez R, Gunthard HF, Garcia S, et al. Host and viral genetic correlates of clinical definitions of HIV-1 disease progression. PLoS ONE. 2010;5(6):e11079.","journal-title":"PLoS ONE"},{"key":"591_CR2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.coviro.2019.05.010","volume":"38","author":"C Lopez-Galindez","year":"2019","unstructured":"Lopez-Galindez C, Pernas M, Casado C, Olivares I, Lorenzo-Redondo R. Elite controllers and lessons learned for HIV-1 cure. Curr Opin Virol. 2019;38:31\u20136.","journal-title":"Curr Opin Virol"},{"issue":"8","key":"591_CR3","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1097\/QAD.0000000000001050","volume":"30","author":"A Leon","year":"2016","unstructured":"Leon A, Perez I, Ruiz-Mateos E, Benito JM, Leal M, Lopez-Galindez C, et al. Rate and predictors of progression in elite and viremic HIV-1 controllers. AIDS. 2016;30(8):1209\u201320.","journal-title":"AIDS"},{"issue":"1","key":"591_CR4","doi-asserted-by":"crossref","first-page":"e41","DOI":"10.1016\/S2352-3018(14)70016-5","volume":"1","author":"JJ van der Helm","year":"2014","unstructured":"van der Helm JJ, Geskus R, Lodi S, Meyer L, Schuitemaker H, Gunsenheimer-Bartmeyer B, et al. Characterisation of long-term non-progression of HIV-1 infection after seroconversion: a cohort study. Lancet HIV. 2014;1(1):e41\u20138.","journal-title":"Lancet HIV"},{"issue":"4","key":"591_CR5","doi-asserted-by":"crossref","first-page":"e0173893","DOI":"10.1371\/journal.pone.0173893","volume":"12","author":"F Chereau","year":"2017","unstructured":"Chereau F, Madec Y, Sabin C, Obel N, Ruiz-Mateos E, Chrysos G, et al. Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers. PLoS ONE. 2017;12(4):e0173893.","journal-title":"PLoS ONE"},{"issue":"10","key":"591_CR6","doi-asserted-by":"crossref","first-page":"e77663","DOI":"10.1371\/journal.pone.0077663","volume":"8","author":"C Casado","year":"2013","unstructured":"Casado C, Pernas M, Sandonis V, Alvaro-Cifuentes T, Olivares I, Fuentes R, et al. Identification of a cluster of HIV-1 controllers infected with low replicating viruses. PLoS ONE. 2013;8(10):e77663.","journal-title":"PLoS ONE"},{"issue":"15","key":"591_CR7","doi-asserted-by":"crossref","first-page":"7581","DOI":"10.1128\/JVI.00286-10","volume":"84","author":"T Miura","year":"2010","unstructured":"Miura T, Brumme ZL, Brockman MA, Rosato P, Sela J, Brumme CJ, et al. Impaired replication capacity of acute\/early viruses in persons who become HIV controllers. J Virol. 2010;84(15):7581\u201391.","journal-title":"J Virol"},{"issue":"5","key":"591_CR8","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1128\/JVI.02165-06","volume":"81","author":"JN Blankson","year":"2007","unstructured":"Blankson JN, Bailey JR, Thayil S, Yang HC, Lassen K, Lai J, et al. Isolation and characterization of replication-competent human immunodeficiency virus type 1 from a subset of elite suppressors. J Virol. 2007;81(5):2508\u201318.","journal-title":"J Virol"},{"issue":"7018","key":"591_CR9","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nature03113","volume":"432","author":"P Kiepiela","year":"2004","unstructured":"Kiepiela P, Leslie AJ, Honeyborne I, Ramduth D, Thobakgale C, Chetty S, et al. Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature. 2004;432(7018):769\u201375.","journal-title":"Nature"},{"issue":"6010","key":"591_CR10","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1126\/science.1195271","volume":"330","author":"F Pereyra","year":"2010","unstructured":"Pereyra F, Jia X, McLaren PJ, Telenti A, de Bakker PI, Walker BD, et al. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science. 2010;330(6010):1551\u20137.","journal-title":"Science"},{"issue":"22","key":"591_CR11","doi-asserted-by":"crossref","first-page":"11937","DOI":"10.1128\/JVI.01086-10","volume":"84","author":"MA Brockman","year":"2010","unstructured":"Brockman MA, Brumme ZL, Brumme CJ, Miura T, Sela J, Rosato PC, et al. Early selection in Gag by protective HLA alleles contributes to reduced HIV-1 replication capacity that may be largely compensated for in chronic infection. J Virol. 2010;84(22):11937\u201349.","journal-title":"J Virol"},{"issue":"7","key":"591_CR12","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.1128\/JVI.80.7.3617-3623.2006","volume":"80","author":"J Martinez-Picado","year":"2006","unstructured":"Martinez-Picado J, Prado JG, Fry EE, Pfafferott K, Leslie A, Chetty S, et al. Fitness cost of escape mutations in p24 Gag in association with control of human immunodeficiency virus type 1. J Virol. 2006;80(7):3617\u201323.","journal-title":"J Virol"},{"issue":"2","key":"591_CR13","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1128\/JVI.01882-08","volume":"83","author":"JG Prado","year":"2009","unstructured":"Prado JG, Honeyborne I, Brierley I, Puertas MC, Martinez-Picado J, Goulder PJ. Functional consequences of human immunodeficiency virus escape from an HLA-B*13-restricted CD8+ T-cell epitope in p1 Gag protein. J Virol. 2009;83(2):1018\u201325.","journal-title":"J Virol"},{"issue":"15","key":"591_CR14","doi-asserted-by":"crossref","first-page":"6818","DOI":"10.1128\/JVI.00276-16","volume":"90","author":"CK Koofhethile","year":"2016","unstructured":"Koofhethile CK, Ndhlovu ZM, Thobakgale-Tshabalala C, Prado JG, Ismail N, Mncube Z, et al. CD8+ T cell breadth and ex vivo virus inhibition capacity distinguish between viremic controllers with and without protective HLA class I alleles. J Virol. 2016;90(15):6818\u201331.","journal-title":"J Virol"},{"key":"591_CR15","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00544-17","author":"EM Leitman","year":"2017","unstructured":"Leitman EM, Willberg CB, Tsai MH, Chen H, Buus S, Chen F, et al. HLA-B*14:02-restricted env-specific CD8(+) T-cell activity has highly potent antiviral efficacy associated with immune control of HIV infection. J Virol. 2017. https:\/\/doi.org\/10.1128\/JVI.00544-17.","journal-title":"J Virol"},{"issue":"2","key":"591_CR16","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1084\/jem.193.2.181","volume":"193","author":"PJ Goulder","year":"2001","unstructured":"Goulder PJ, Altfeld MA, Rosenberg ES, Nguyen T, Tang Y, Eldridge RL, et al. Substantial differences in specificity of HIV-specific cytotoxic T cells in acute and chronic HIV infection. J Exp Med. 2001;193(2):181\u201394.","journal-title":"J Exp Med"},{"issue":"4","key":"591_CR17","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1084\/jem.175.4.961","volume":"175","author":"RP Johnson","year":"1992","unstructured":"Johnson RP, Trocha A, Buchanan TM, Walker BD. Identification of overlapping HLA class I-restricted cytotoxic T cell epitopes in a conserved region of the human immunodeficiency virus type 1 envelope glycoprotein: definition of minimum epitopes and analysis of the effects of sequence variation. J Exp Med. 1992;175(4):961\u201371.","journal-title":"J Exp Med"},{"issue":"13","key":"591_CR18","doi-asserted-by":"crossref","first-page":"8171","DOI":"10.1128\/JVI.79.13.8171-8181.2005","volume":"79","author":"T Koibuchi","year":"2005","unstructured":"Koibuchi T, Allen TM, Lichterfeld M, Mui SK, O\u2019Sullivan KM, Trocha A, et al. Limited sequence evolution within persistently targeted CD8 epitopes in chronic human immunodeficiency virus type 1 infection. J Virol. 2005;79(13):8171\u201381.","journal-title":"J Virol"},{"issue":"2","key":"591_CR19","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1097\/QAI.0b013e31816b6abd","volume":"48","author":"KS Kemal","year":"2008","unstructured":"Kemal KS, Beattie T, Dong T, Weiser B, Kaul R, Kuiken C, et al. Transition from long-term nonprogression to HIV-1 disease associated with escape from cellular immune control. J Acquir Immune Defic Syndr. 2008;48(2):119\u201326.","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"6","key":"591_CR20","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1086\/520885","volume":"196","author":"C Casado","year":"2007","unstructured":"Casado C, Pernas M, Alvaro T, Sandonis V, Garcia S, Rodriguez C, et al. Coinfection and superinfection in patients with long-term, nonprogressive HIV-1 disease. J Infect Dis. 2007;196(6):895\u20139.","journal-title":"J Infect Dis"},{"issue":"2","key":"591_CR21","doi-asserted-by":"crossref","first-page":"e1001273","DOI":"10.1371\/journal.ppat.1001273","volume":"7","author":"G Ferrari","year":"2011","unstructured":"Ferrari G, Korber B, Goonetilleke N, Liu MK, Turnbull EL, Salazar-Gonzalez JF, et al. Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection. PLoS Pathog. 2011;7(2):e1001273.","journal-title":"PLoS Pathog"},{"issue":"1","key":"591_CR22","first-page":"380","volume":"123","author":"MK Liu","year":"2013","unstructured":"Liu MK, Hawkins N, Ritchie AJ, Ganusov VV, Whale V, Brackenridge S, et al. Vertical T cell immunodominance and epitope entropy determine HIV-1 escape. J Clin Invest. 2013;123(1):380\u201393.","journal-title":"J Clin Invest"},{"issue":"15","key":"591_CR23","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1089\/088922201753197060","volume":"17","author":"G Fang","year":"2001","unstructured":"Fang G, Burger H, Chappey C, Rowland-Jones S, Visosky A, Chen CH, et al. Analysis of transition from long-term nonprogressive to progressive infection identifies sequences that may attenuate HIV type 1. AIDS Res Hum Retroviruses. 2001;17(15):1395\u2013404.","journal-title":"AIDS Res Hum Retroviruses"},{"issue":"2","key":"591_CR24","doi-asserted-by":"crossref","first-page":"e31928","DOI":"10.1371\/journal.pone.0031928","volume":"7","author":"M Pernas","year":"2012","unstructured":"Pernas M, Casado C, Arcones C, Llano A, Sanchez-Merino V, Mothe B, et al. Low-replicating viruses and strong anti-viral immune response associated with prolonged disease control in a superinfected HIV-1 LTNP elite controller. PLoS ONE. 2012;7(2):e31928.","journal-title":"PLoS ONE"},{"issue":"15","key":"591_CR25","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1097\/01.aids.0000431945.72365.01","volume":"27","author":"Y Madec","year":"2013","unstructured":"Madec Y, Boufassa F, Porter K, Prins M, Sabin C, D\u2019Arminio MA, et al. Natural history of HIV-control since seroconversion. AIDS. 2013;27(15):2451\u201360.","journal-title":"AIDS"},{"key":"591_CR26","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01805-17","author":"M Pernas","year":"2018","unstructured":"Pernas M, Tarancon-Diez L, Rodriguez-Gallego E, Gomez J, Prado JG, Casado C, et al. Factors Leading to the Loss of Natural Elite Control of HIV-1 Infection. J Virol. 2018. https:\/\/doi.org\/10.1128\/JVI.01805-17.","journal-title":"J Virol"},{"issue":"9","key":"591_CR27","doi-asserted-by":"crossref","first-page":"e0184929","DOI":"10.1371\/journal.pone.0184929","volume":"12","author":"M Rosas-Umbert","year":"2017","unstructured":"Rosas-Umbert M, Mothe B, Noguera-Julian M, Bellido R, Puertas MC, Carrillo J, et al. Virological and immunological outcome of treatment interruption in HIV-1-infected subjects vaccinated with MVA-B. PLoS ONE. 2017;12(9):e0184929.","journal-title":"PLoS ONE"},{"issue":"10","key":"591_CR28","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1016\/j.immuni.2021.08.007","volume":"54","author":"DR Collins","year":"2021","unstructured":"Collins DR, Urbach JM, Racenet ZJ, Arshad U, Power KA, Newman RM, et al. Functional impairment of HIV-specific CD8(+) T cells precedes aborted spontaneous control of viremia. Immunity. 2021;54(10):2372\u201384.","journal-title":"Immunity"},{"issue":"1","key":"591_CR29","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1186\/s12879-019-4229-3","volume":"19","author":"DG Caetano","year":"2019","unstructured":"Caetano DG, Cortes FH, Bello G, de Azevedo SSD, Hoagland B, Villela LM, et al. A case report of HIV-1 superinfection in an HIV controller leading to loss of viremia control: a retrospective of 10 years of follow-up. BMC Infect Dis. 2019;19(1):588.","journal-title":"BMC Infect Dis"},{"issue":"4","key":"591_CR30","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.jcv.2010.01.013","volume":"47","author":"O Clerc","year":"2010","unstructured":"Clerc O, Colombo S, Yerly S, Telenti A, Cavassini M. HIV-1 elite controllers: beware of super-infections. J Clin Virol. 2010;47(4):376\u20138.","journal-title":"J Clin Virol"},{"issue":"11","key":"591_CR31","doi-asserted-by":"crossref","first-page":"e86","DOI":"10.1086\/592978","volume":"47","author":"A Rachinger","year":"2008","unstructured":"Rachinger A, Navis M, van Assen S, Groeneveld PH, Schuitemaker H. Recovery of viremic control after superinfection with pathogenic HIV type 1 in a long-term elite controller of HIV type 1 infection. Clin Infect Dis. 2008;47(11):e86\u20139.","journal-title":"Clin Infect Dis"},{"issue":"3","key":"591_CR32","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1097\/QAI.0b013e31829bdc85","volume":"64","author":"M Pernas","year":"2013","unstructured":"Pernas M, Casado C, Sandonis V, Arcones C, Rodriguez C, Ruiz-Mateos E, et al. Prevalence of HIV-1 dual infection in long-term nonprogressor-elite controllers. J Acquir Immune Defic Syndr. 2013;64(3):225\u201331.","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"12","key":"591_CR33","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/nm1295-1284","volume":"1","author":"TW Chun","year":"1995","unstructured":"Chun TW, Finzi D, Margolick J, Chadwick K, Schwartz D, Siliciano RF. In vivo fate of HIV-1-infected T cells: quantitative analysis of the transition to stable latency. Nat Med. 1995;1(12):1284\u201390.","journal-title":"Nat Med"},{"issue":"11","key":"591_CR34","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1097\/00002030-199907300-00023","volume":"13","author":"JE Mittler","year":"1999","unstructured":"Mittler JE, Markowitz M, Ho DD, Perelson AS. Improved estimates for HIV-1 clearance rate and intracellular delay. AIDS. 1999;13(11):1415\u20137.","journal-title":"AIDS"},{"issue":"3","key":"591_CR35","doi-asserted-by":"crossref","first-page":"e1006283","DOI":"10.1371\/journal.ppat.1006283","volume":"13","author":"JK Bui","year":"2017","unstructured":"Bui JK, Sobolewski MD, Keele BF, Spindler J, Musick A, Wiegand A, et al. Proviruses with identical sequences comprise a large fraction of the replication-competent HIV reservoir. PLoS Pathog. 2017;13(3):e1006283.","journal-title":"PLoS Pathog"},{"issue":"9","key":"591_CR36","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/nm.4156","volume":"22","author":"KM Bruner","year":"2016","unstructured":"Bruner KM, Murray AJ, Pollack RA, Soliman MG, Laskey SB, Capoferri AA, et al. Defective proviruses rapidly accumulate during acute HIV-1 infection. Nat Med. 2016;22(9):1043\u20139.","journal-title":"Nat Med"},{"issue":"12","key":"591_CR37","doi-asserted-by":"crossref","first-page":"6742","DOI":"10.1128\/JVI.00022-07","volume":"81","author":"AJ Frater","year":"2007","unstructured":"Frater AJ, Brown H, Oxenius A, Gunthard HF, Hirschel B, Robinson N, et al. Effective T-cell responses select human immunodeficiency virus mutants and slow disease progression. J Virol. 2007;81(12):6742\u201351.","journal-title":"J Virol"},{"issue":"2","key":"591_CR38","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1006\/viro.1997.8996","volume":"241","author":"R Shankarappa","year":"1998","unstructured":"Shankarappa R, Gupta P, Learn GH Jr, Rodrigo AG, Rinaldo CR Jr, Gorry MC, et al. Evolution of human immunodeficiency virus type 1 envelope sequences in infected individuals with differing disease progression profiles. Virology. 1998;241(2):251\u20139.","journal-title":"Virology"},{"issue":"1","key":"591_CR39","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/nrg1246","volume":"5","author":"A Rambaut","year":"2004","unstructured":"Rambaut A, Posada D, Crandall KA, Holmes EC. The causes and consequences of HIV evolution. Nat Rev Genet. 2004;5(1):52\u201361.","journal-title":"Nat Rev Genet"},{"issue":"11","key":"591_CR40","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1097\/QAD.0b013e3283021a8c","volume":"22","author":"ZL Brumme","year":"2008","unstructured":"Brumme ZL, Tao I, Szeto S, Brumme CJ, Carlson JM, Chan D, et al. Human leukocyte antigen-specific polymorphisms in HIV-1 Gag and their association with viral load in chronic untreated infection. AIDS. 2008;22(11):1277\u201386.","journal-title":"AIDS"},{"issue":"5","key":"591_CR41","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1128\/jvi.76.5.2298-2305.2002","volume":"76","author":"BH Edwards","year":"2002","unstructured":"Edwards BH, Bansal A, Sabbaj S, Bakari J, Mulligan MJ, Goepfert PA. Magnitude of functional CD8+ T-cell responses to the gag protein of human immunodeficiency virus type 1 correlates inversely with viral load in plasma. J Virol. 2002;76(5):2298\u2013305.","journal-title":"J Virol"},{"issue":"1","key":"591_CR42","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/nm1520","volume":"13","author":"P Kiepiela","year":"2007","unstructured":"Kiepiela P, Ngumbela K, Thobakgale C, Ramduth D, Honeyborne I, Moodley E, et al. CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat Med. 2007;13(1):46\u201353.","journal-title":"Nat Med"},{"issue":"5","key":"591_CR43","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1097\/QAD.0b013e328328f76e","volume":"23","author":"A Piantadosi","year":"2009","unstructured":"Piantadosi A, Chohan B, Panteleeff D, Baeten JM, Mandaliya K, Ndinya-Achola JO, et al. HIV-1 evolution in gag and env is highly correlated but exhibits different relationships with viral load and the immune response. AIDS. 2009;23(5):579\u201387.","journal-title":"AIDS"},{"issue":"3","key":"591_CR44","doi-asserted-by":"crossref","first-page":"e1002529","DOI":"10.1371\/journal.ppat.1002529","volume":"8","author":"MR Henn","year":"2012","unstructured":"Henn MR, Boutwell CL, Charlebois P, Lennon NJ, Power KA, Macalalad AR, et al. Whole genome deep sequencing of HIV-1 reveals the impact of early minor variants upon immune recognition during acute infection. PLoS Pathog. 2012;8(3):e1002529.","journal-title":"PLoS Pathog"},{"issue":"19","key":"591_CR45","doi-asserted-by":"crossref","first-page":"9519","DOI":"10.1128\/JVI.00575-06","volume":"80","author":"Y Liu","year":"2006","unstructured":"Liu Y, McNevin J, Cao J, Zhao H, Genowati I, Wong K, et al. Selection on the human immunodeficiency virus type 1 proteome following primary infection. J Virol. 2006;80(19):9519\u201329.","journal-title":"J Virol"},{"issue":"11","key":"591_CR46","doi-asserted-by":"crossref","first-page":"7131","DOI":"10.4049\/jimmunol.0803658","volume":"182","author":"EL Turnbull","year":"2009","unstructured":"Turnbull EL, Wong M, Wang S, Wei X, Jones NA, Conrod KE, et al. Kinetics of expansion of epitope-specific T cell responses during primary HIV-1 infection. J Immunol. 2009;182(11):7131\u201345.","journal-title":"J Immunol"},{"issue":"1","key":"591_CR47","doi-asserted-by":"crossref","first-page":"120S","DOI":"10.1042\/bst025120s","volume":"25","author":"CA Burgess","year":"1997","unstructured":"Burgess CA, Grant GH. Compensatory mutations and protein stability: a theoretical study. Biochem Soc Trans. 1997;25(1):120S.","journal-title":"Biochem Soc Trans"},{"issue":"4","key":"591_CR48","doi-asserted-by":"crossref","first-page":"e1000365","DOI":"10.1371\/journal.ppat.1000365","volume":"5","author":"RM Troyer","year":"2009","unstructured":"Troyer RM, McNevin J, Liu Y, Zhang SC, Krizan RW, Abraha A, et al. Variable fitness impact of HIV-1 escape mutations to cytotoxic T lymphocyte (CTL) response. PLoS Pathog. 2009;5(4):e1000365.","journal-title":"PLoS Pathog"},{"key":"591_CR49","unstructured":"Hall TA. Bioedit: a user-friendly biological sequence aligment editor and analysis program for Windows 95\/98\/NT. 1999. London, Information Retrieval Ltd. Ref Type: Generic"},{"issue":"12","key":"591_CR50","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1093\/molbev\/mst197","volume":"30","author":"K Tamura","year":"2013","unstructured":"Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: molecular evolutionary genetics analysis version 60. Mol Biol Evol. 2013;30(12):2725\u20139.","journal-title":"Mol Biol Evol"},{"issue":"1","key":"591_CR51","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.virol.2009.05.022","volume":"391","author":"V Sandonis","year":"2009","unstructured":"Sandonis V, Casado C, Alvaro T, Pernas M, Olivares I, Garcia S, et al. A combination of defective DNA and protective host factors are found in a set of HIV-1 ancestral LTNPs. Virology. 2009;391(1):73\u201382.","journal-title":"Virology"},{"issue":"3","key":"591_CR52","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1128\/JVI.77.3.2081-2092.2003","volume":"77","author":"MM Addo","year":"2003","unstructured":"Addo MM, Yu XG, Rathod A, Cohen D, Eldridge RL, Strick D, et al. Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load. J Virol. 2003;77(3):2081\u201392.","journal-title":"J Virol"},{"issue":"9","key":"591_CR53","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1097\/QAD.0000000000000293","volume":"28","author":"J Dalmau","year":"2014","unstructured":"Dalmau J, Rotger M, Erkizia I, Rauch A, Reche P, Pino M, et al. Highly pathogenic adapted HIV-1 strains limit host immunity and dictate rapid disease progression. AIDS. 2014;28(9):1261\u201372.","journal-title":"AIDS"},{"issue":"1 Pt 1","key":"591_CR54","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/0092-8674(80)90178-6","volume":"22","author":"M Perucho","year":"1980","unstructured":"Perucho M, Hanahan D, Wigler M. Genetic and physical linkage of exogenous sequences in transformed cells. Cell. 1980;22(1 Pt 1):309\u201317.","journal-title":"Cell"},{"issue":"W1","key":"591_CR55","doi-asserted-by":"crossref","first-page":"W296","DOI":"10.1093\/nar\/gky427","volume":"46","author":"A Waterhouse","year":"2018","unstructured":"Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, et al. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 2018;46(W1):W296\u2013303.","journal-title":"Nucleic Acids Res"},{"issue":"11","key":"591_CR56","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1110\/ps.062416606","volume":"15","author":"MY Shen","year":"2006","unstructured":"Shen MY, Sali A. Statistical potential for assessment and prediction of protein structures. Protein Sci. 2006;15(11):2507\u201324.","journal-title":"Protein Sci"},{"issue":"47","key":"591_CR57","first-page":"5","volume":"8","author":"B Webb","year":"2014","unstructured":"Webb B, Sali A. Comparative protein structure modeling using MODELLER. Curr Protoc Bioinformatics. 2014;8(47):5\u201332.","journal-title":"Curr Protoc Bioinformatics"},{"issue":"23","key":"591_CR58","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.1093\/bioinformatics\/btt530","volume":"29","author":"M Arenas","year":"2013","unstructured":"Arenas M, Dos Santos HG, Posada D, Bastolla U. Protein evolution along phylogenetic histories under structurally constrained substitution models. Bioinformatics. 2013;29(23):3020\u20138.","journal-title":"Bioinformatics"}],"container-title":["Retrovirology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12977-022-00591-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12977-022-00591-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12977-022-00591-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T04:48:49Z","timestamp":1648529329000},"score":1,"resource":{"primary":{"URL":"https:\/\/retrovirology.biomedcentral.com\/articles\/10.1186\/s12977-022-00591-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,26]]},"references-count":58,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["591"],"URL":"https:\/\/doi.org\/10.1186\/s12977-022-00591-7","relation":{},"ISSN":["1742-4690"],"issn-type":[{"type":"electronic","value":"1742-4690"}],"subject":[],"published":{"date-parts":[[2022,3,26]]},"assertion":[{"value":"14 December 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 March 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The individual provided a written informed consent for research purposes of biological samples following the guidelines of the institutional ethical committees of the Institute of Salud Carlos III (CEI PI 05-2010-v3).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All the authors revised and approved the final version of the manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that there is no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6"}}