dc.contributor.author | Moyano, Ana | |
dc.contributor.author | Blanch-Lombarte, Oscar | |
dc.contributor.author | Tarancon-Diez, Laura | |
dc.contributor.author | Pedreño-Lopez, Nuria | |
dc.contributor.author | Arenas, Miguel | |
dc.contributor.author | Alvaro-Cifuentes, Tamara | |
dc.contributor.author | Casado, Concepcion | |
dc.contributor.author | Olivares, Isabel | |
dc.contributor.author | Vera, Mar | |
dc.contributor.author | Rodriguez, Carmen | |
dc.contributor.author | Del Romero, Jorge | |
dc.contributor.author | Lopez-Galindez, Luis Cecilio | |
dc.contributor.author | Ruiz-Mateos, Ezequiel | |
dc.contributor.author | Prado, Julia G | |
dc.contributor.author | Pernas, Maria | |
dc.date.accessioned | 2022-05-24T10:43:25Z | |
dc.date.available | 2022-05-24T10:43:25Z | |
dc.date.issued | 2022-03-26 | |
dc.identifier.citation | Retrovirology. 2022 Mar 26;19(1):6. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/14484 | |
dc.description.abstract | Background: 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 + T-cell counts. Control of HIV-1 infection in LTNPs viremic controllers, have been associated with effective immunodominant HIV-1 Gag-CD8 + T-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 + T-cell response. Limited data are available on the contribution of HLA-B*14:02 CD8 + T -cells in LTNPs. Results: 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 years after HIV-1 diagnosis. We analysed viral evolution and immune escape in HLA-B*14:02 restricted CD8 + T -cell epitopes and identified viral evolution at the Env-EL9 epitope selecting the L592R mutation. By IFN-γ ELISpot and immune phenotype, we characterized HLA- B*14:02 HIV-1 CD8 + T 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 + cell response over time with LVC. Loss of Env-EL9 responses was concomitant with selecting K588R + L592R mutations at Env-EL9. Finally, we evaluated the impact of Env-EL9 escape mutations on HIV-1 infectivity and Env protein structure. The K588R + L592R escape variant was directly related to HIV-1 increase replicative capacity and stability of Env at the LVC. Conclusions: These findings support the contribution of immunodominant Env-EL9 CD8 + T-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 + T-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 + T-cell responses. | es_ES |
dc.description.sponsorship | Molecular Virology Laboratory was supported by grants SAF (2016-77894-R) from Ministerio de Economía y Competitividad (MINECO), ISCIII through the projects PI 13/02269, PI17/00164, PI16/0684, PI19/01127 (Co-funded by European Regional Development Fund/European Social Fund "Investing in your future"). The RIS-RETIC grants RD12/0017/0028, RD16/0025/0020 and RD16CIII/0002/0005. LTD was supported by the Instituto de Salud Carlos III (ISCIII) under grant agreement “CD20/00025” through the Sara Borrell Program. O.B.L was funded by an AGAUR-FI_B 00582 Ph.D. fellowship from the Catalan Government and the European Social Fund. M.A. was funded by grants RYC-2015-18241 and PID2019-107931GA-I00 from the Spanish Government and, ED431F 2018/08 from the “Xunta de Galicia”. ERM was supported by the Spanish National Research Council (CSIC). JGP laboratory was supported by National Health Institute Carlos III grant PI17/00164 and Redes Temáticas de Investigación en SIDA (ISCIII RETIC RD16/0025/0041). The funders had no role in study design, data collection and analysis, the decision to publish or drafting of the manuscript. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | BioMed Central (BMC) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | CD8 + T-cells | es_ES |
dc.subject | Env-EL9 escape HLA-B*14:02 | es_ES |
dc.subject | Long-term non-progressor (LTNP) | es_ES |
dc.subject | Loss of viral control (LVC) | es_ES |
dc.title | Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 35346235 | es_ES |
dc.format.volume | 19 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 6 | es_ES |
dc.identifier.doi | 10.1186/s12977-022-00591-7 | es_ES |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | es_ES |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | es_ES |
dc.contributor.funder | Unión Europea. Fondo Social Europeo (ESF/FSE) | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) | es_ES |
dc.contributor.funder | Government of Catalonia (España) | es_ES |
dc.contributor.funder | Government of Spain | es_ES |
dc.contributor.funder | Xunta de Galicia (España) | es_ES |
dc.contributor.funder | Consejo Superior de Investigaciones Científicas (España) | es_ES |
dc.contributor.funder | RETICS-Sida (RIS-ISCIII) (España) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1742-4690 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1186/s12977-022-00591-7 | es_ES |
dc.identifier.journal | Retrovirology | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/SAF-2016-77894 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RD12/0017/0028 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/MINECO//RD16%2F0025%2F0020/ES/RED ESPAÑOLA DE INVESTIGACIÓN EN SIDA (RIS)/ | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2019-107931GA-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/MINECO//RD16%2F0025%2F0041/ES/RED ESPAÑOLA DE INVESTIGACIÓN EN SIDA (RIS)/ | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/PI13/02269 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/PI17/00164 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/PI16/0684 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/PI19/01127 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/CD20/00025 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/RD16CIII/0002/0005 | es_ES |