RT Journal Article T1 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 A1 Moyano, Ana A1 Blanch Lombarte, Oscar A1 Tarancón Diez, Laura A1 Pedreño Lopez, Nuria A1 Arenas Busto, Miguel A1 Alvaro, Tamara A1 Casado, Concepción A1 Olivares, Isabel A1 Vera, Mar A1 Rodríguez, Carmen A1 del Romero, Jorge A1 López Galíndez, Cecilio A1 Ruiz Mateos, Ezequiel A1 Prado, Julia G. A1 Pernas, María K1 2409 Genética K1 2403 Bioquímica K1 2420 Virología AB 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. PB Retrovirology SN 17424690 YR 2022 FD 2022-03-26 LK http://hdl.handle.net/11093/6492 UL http://hdl.handle.net/11093/6492 LA eng NO Retrovirology, 19: 6 (2022) NO Instituto de Salud Carlos III | Ref. PI13/02269 DS Investigo RD 08-feb-2025