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
Por:
Moyano, A, Blanch-Lombarte, O, Tarancon-Diez, L, Pedreno-Lopez, N, Arenas, M, Alvaro, T, Casado, C, Olivares, I, Vera, M, Rodriguez, C, del Romero, J, Lopez-Galindez, C, Ruiz-Mateos, E, Prado, JG and Pernas, M
Publicada:
26 mar 2022
Resumen:
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-gamma 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.
Filiaciones:
Moyano, A:
Inst Salud Carlos III, Ctr Nacl Microbiol, Lab Referencia & Invest Retrovirus, Virol Mol, Carretera Pozuelo Majadahonda Km 2, Madrid 28220, Spain
LMU Munchen, Max Von Pettenkofer Inst & Gene Ctr, Natl Reference Ctr Retroviruses, Virol,Fac Med, Munich, Germany
:
IrsiCaixa AIDS Res Inst, Crta Canyet SN, Barcelona 08916, Spain
Autonomous Univ Barcelona, Barcelona, Spain
Tarancon-Diez, L:
Univ Seville, Virgen del Rocio Univ Hosp, CSIC, Inst Biomed Seville IBiS, Seville, Spain
Hosp Gregorio Maranon, Immunol Sect, Mol Immunobiol Lab, Madrid, Spain
:
Inst Salud Carlos III, Ctr Nacl Microbiol, Lab Referencia & Invest Retrovirus, Virol Mol, Carretera Pozuelo Majadahonda Km 2, Madrid 28220, Spain
IrsiCaixa AIDS Res Inst, Crta Canyet SN, Barcelona 08916, Spain
Arenas, M:
Univ Vigo, Dept Biochem Genet & Immunol, Vigo 36310, Spain
Univ Vigo, CINBIO, Vigo 36310, Spain
Galicia Sur Hlth Res Inst IIS Galicia Sur, Vigo 36310, Spain
Alvaro, T:
Inst Salud Carlos III, Ctr Nacl Microbiol, Lab Referencia & Invest Retrovirus, Virol Mol, Carretera Pozuelo Majadahonda Km 2, Madrid 28220, Spain
Casado, C:
Inst Salud Carlos III, Ctr Nacl Microbiol, Lab Referencia & Invest Retrovirus, Virol Mol, Carretera Pozuelo Majadahonda Km 2, Madrid 28220, Spain
Olivares, I:
Inst Salud Carlos III, Ctr Nacl Microbiol, Lab Referencia & Invest Retrovirus, Virol Mol, Carretera Pozuelo Majadahonda Km 2, Madrid 28220, Spain
Vera, M:
Hosp Clin San Carlos, IdISSC, Ctr Sanitario Sandoval, Madrid, Spain
Rodriguez, C:
Hosp Clin San Carlos, IdISSC, Ctr Sanitario Sandoval, Madrid, Spain
del Romero, J:
Hosp Clin San Carlos, IdISSC, Ctr Sanitario Sandoval, Madrid, Spain
Lopez-Galindez, C:
Inst Salud Carlos III, Ctr Nacl Microbiol, Lab Referencia & Invest Retrovirus, Virol Mol, Carretera Pozuelo Majadahonda Km 2, Madrid 28220, Spain
Ruiz-Mateos, E:
LMU Munchen, Max Von Pettenkofer Inst & Gene Ctr, Natl Reference Ctr Retroviruses, Virol,Fac Med, Munich, Germany
:
IrsiCaixa AIDS Res Inst, Crta Canyet SN, Barcelona 08916, Spain
Germans Trias & Pujol Res Inst IGTP, Badalona, Spain
Pernas, M:
Inst Salud Carlos III, Ctr Nacl Microbiol, Lab Referencia & Invest Retrovirus, Virol Mol, Carretera Pozuelo Majadahonda Km 2, Madrid 28220, Spain
gold, Green Published
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