P16-37. HIV controllers with weak CD8+ T cell responses maintain a tight control of infection despite carrying infectious viruses

Sáez‐Cirión, Asier; Sinet, Martine; Shin, So Youn; Urrutia, Alejandra; Versmisse, Pierre; Boufassa, Faroudy; Rouzioux, C; Lambotte, O.; Venet, Alain; Pancino, Gianfranco

doi:10.1186/1742-4690-6-s3-p266

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“…Evidence in macaques have shown that SIV viral load and proviral DNA were rapidly increased after CD8 depletion in vivo (112,113) and decreased when CD8 + cells returning back (9). Studies in ex vivo and in vitro also present an ability of CD8 + T cells to suppress viral replication as seen in animal model (114)(115)(116). HIV Gag-specific CD8 + T cell response is associated with low plasma viral load (117)(118)(119)(120).…”

Section: Adaptive Immunitymentioning

confidence: 98%

“…Studies in ex vivo and in vitro also present an ability of CD8 + T cells to suppress viral replication as seen in animal model (114)(115)(116). HIV Gag-specific CD8 + T cell response is associated with low plasma viral load (117)(118)(119)(120). Polyfunctionality such as MIP-1β, IFNγ, TNFα, CD107a as degranulation marker and IL-2 (11,121) and effective proliferative capacity (122) have been remarked in HIV controllers.…”

Section: Adaptive Immunitymentioning

confidence: 99%

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CTL-mediated immune evasion in hiv viraemic controllers and non-controllers

Kaewpreedee

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Objective:?To compare T cell response and to identify the mechanism of escape in HIV-infected volunteers. Methods:?HIV-infected volunteers (CD4>450 cells/?L) were enrolled from the?anonymous clinic. Volunteers were classified into two groups based on HIV plasma viral load; viraemic controllers (VC) (VL<2000 cp/mL) and non-controllers (NC) (VL>2000 cp/mL). EDTA-whole blood was collected and determined?the response?against Gag p24 by IFN? ELISpot assay. Population sequencing within the Gag p24 region was performed to identify escape mutations. Results: Demographic data [age, gender, sexual preference and the presence of protective alleles (HLA-B27, -B57 and ?B58)]?between VC (n=23) and NC (n=41) were no statistical significance. IFN?-secreting cells?response against Gag p24 as determining?by?ELISpot assay revealed that some volunteers could not respond to?epitopes which are restricted by?their HLA alleles (termed as non-responder). The HLA-B27-KK10 non-responders contain HLA polymorphism, HLA-B2706 which accommodates different amino acid with HLA-B2704 and HLA-B2705. The HLA-B57-TW10 and QW9, non-responders did not respond because escape mutation (T242N and T3S, respectively) was found within non-responders? sequences. Interestingly, HLA-A11-AK11 epitope at the amino acid level was not different among responders and non-responders. Codon usages were subsequently compared and it was found that at the C-terminal position (K; Lysine) preferred different codons for translating to lysine. AAG codon is more preferable in AK11-responders while AAA codon is preferred in AK11 non-responders. In conclusion, these findings may contribute to better knowledge on HIV pathogenesis and the way to improve vaccine efficacy in the future.? ? ?

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