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| Pàgina inicial > Articles > Articles publicats > 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 |
(Universitat Autònoma de Barcelona) (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa) (Instituto de Biomedicina de Sevilla) (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)| Data: | 2022 |
| Resum: | 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. 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. 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. The online version contains supplementary material available at 10. 1186/s12977-022-00591-7. |
| Ajuts: | Instituto de Salud Carlos III CD20/00025 Instituto de Salud Carlos III PI13/02269 Instituto de Salud Carlos III PI17/00164 Instituto de Salud Carlos III PI16/0684 Instituto de Salud Carlos III PI19/01127 Instituto de Salud Carlos III PI17/00164 Ministerio de Economía y Competitividad RYC-2015-18241 Agencia Estatal de Investigación PID2019-107931GA-I00 Ministerio de Economía, Industria y Competitividad SAF2016-77894-R Instituto de Salud Carlos III RD12/0017/0028 Instituto de Salud Carlos III RD16/0025/0020 Instituto de Salud Carlos III RD16CIII/0002/0005 Instituto de Salud Carlos III RD16/0025/0041 Agència de Gestió d'Ajuts Universitaris i de Recerca FIB00582 |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Long-term non-progressor (LTNP) ; Loss of viral control (LVC) ; Env-EL9 escape HLA-B*14:02 ; CD8 + T-cells |
| Publicat a: | Retrovirology, Vol. 19 (march 2022) , ISSN 1742-4690 |
