Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B14:02 in a Non progressor who lost twenty-seven years of HIV-1 control

• Published in: Retrovirology Vol. 19; no. 1; p. 6
• Main Authors: Moyano, Ana, Blanch-Lombarte, Oscar, Tarancon-Diez, Laura, Pedreño-Lopez, Nuria, Arenas, Miguel, Alvaro, Tamara, Casado, Concepción, Olivares, Isabel, Vera, Mar, Rodriguez, Carmen, Del Romero, Jorge, López-Galíndez, Cecilio, Ruiz-Mateos, Ezequiel, Prado, Julia G, Pernas, María
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 26.03.2022; BioMed Central; BMC
• Subjects: Analysis; Antigenic determinants; CD4 antigen; CD8 antigen; CD8-Positive T-Lymphocytes; CD8 + T-cells; Control; Development and progression; Env-EL9 escape HLA-B14:02; Enzyme-linked immunosorbent assay; Epitopes; Evolution; Gag protein; Genetic testing; Health aspects; Histocompatibility antigen HLA; Histocompatibility antigens; HIV; HIV (Viruses); HIV Infections - immunology; HIV-1 - physiology; HLA histocompatibility antigens; HLA-B Antigens - genetics; Human immunodeficiency virus; Humans; Immune Evasion; Immunology; Infection; Infection control; Infectivity; Long-term non-progressor (LTNP); Loss of viral control (LVC); Lymphocytes T; Mutation; Peptides; Phenotypes; Phylogenetics; Plasma; Protein structure; T cells; Viral envelope proteins; Viral Load; γ-Interferon; Spain; Long-term non-progressor (LTNP); Loss of viral control (LVC); CD8 + T-cells; Env-EL9 escape HLA-B14:02
• ISSN: 1742-4690; 1742-4690
• DOI: 10.1186/s12977-022-00591-7

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.