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首页> 外文期刊>Human vaccines & immunotherapeutics. >Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1 infected subjects
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Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1 infected subjects

机译:HIV-1,FIV和SIV p24蛋白的保守表位被HIV-1感染的受试者识别

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摘要

Cross-reactive peptides on HIV-1 and FIV p24 protein sequences were studied using peripheral blood mononuclear cells (PBMC) from untreated HIV-1-infected long-term survivors (LTS; >10 y of infection without antiretroviral therapy, ART), short-term HIV-1 infected subjects not on ART, and ART-treated HIV-1 infected subjects. IFN-ELISpot and CFSE-proliferation analyses were performed with PBMC using overlapping HIV-1 and FIV p24 peptides. Over half of the HIV-1 infected subjects tested (22/31 or 71%) responded to one or more FIV p24 peptide pools by either IFN or T-cell proliferation analysis. PBMC and T cells from infected subjects in all 3 HIV+ groups predominantly recognized one FIV p24 peptide pool (Fp14) by IFN production and one additional FIV p24 peptide pool (Fp9) by T-cell proliferation analysis. Furthermore, evaluation of overlapping SIV p24 peptide sequences identified conserved epitope(s) on the Fp14/Hp15-counterpart of SIV, Sp14, but none on Fp9-counterpart of SIV, Sp9. The responses to these FIV peptide pools were highly reproducible and persisted throughout 2-4 y of monitoring. Intracellular staining analysis for cytotoxins and phenotyping for CD107a determined that peptide epitopes from Fp9 and Fp14 pools induced cytotoxic T lymphocyte-associated molecules including perforin, granzyme B, granzyme A, and/or expression of CD107a. Selected FIV and corresponding SIV epitopes recognized by HIV-1 infected patients indicate that these protein sequences are evolutionarily conserved on both SIV and HIV-1 (e.g., Hp15:Fp14:Sp14). These studies demonstrate that comparative immunogenicity analysis of HIV-1, FIV, and SIV can identify evolutionarily-conserved T cell-associated lentiviral epitopes, which could be used as a vaccine for prophylaxis or immunotherapy.
机译:使用未经治疗的HIV-1感染的长期幸存者(LTS;感染时间超过10年,未经抗逆转录病毒疗法,ART)治疗的HIV-1和FIV p24蛋白序列的交叉反应肽,研究了短期非ART的长期HIV-1感染者和接受ART治疗的HIV-1感染者。 PBMC使用重叠的HIV-1和FIV p24肽进行IFN-ELISpot和CFSE增殖分析。通过IFN或T细胞增殖分析,超过一半的受HIV-1感染的受试者(22/31或71%)对一种或多种FIV p24肽库有反应。来自所有3个HIV +组中受感染受试者的PBMC和T细胞主要通过IFN产生识别一个FIV p24肽库(Fp14),并通过T细胞增殖分析识别另外一个FIV p24肽库(Fp9)。此外,对重叠的SIV p24肽序列的评估确定了在SIV Sp14的Fp14 / Hp15-对位上保守的抗原决定簇,但在SIV Sp9的Fp9-对端上没有保守的表位。对这些FIV肽库的响应具有很高的可重复性,并且在整个2-4年的监测中持续存在。细胞毒素的细胞内染色分析和CD107a的表型分析确定,来自Fp9和Fp14库的肽表位诱导了与细胞毒性T淋巴细胞相关的分子,包括穿孔素,颗粒酶B,颗粒酶A和/或CD107a的表达。被HIV-1感染患者识别的选定的FIV和相应的SIV表位表明,这些蛋白序列在SIV和HIV-1上都是进化保守的(例如Hp15:Fp14:Sp14)。这些研究表明,对HIV-1,FIV和SIV进行的比较免疫原性分析可以确定与进化相关的T细胞相关慢病毒表位,可以用作预防或免疫疗法的疫苗。

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