Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1 infected subjects.
Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1 infected subjects.
复制标题
HIV-1、FIV 和 SIV p24 蛋白上的保守表位可被 HIV-1 感染者识别。
DOI：
10.1080/21645515.2015.1026500
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发表时间：
2015
影响因子：
4.8
通讯作者：
Yamamoto,JanetK
中科院分区：
文献类型：
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作者：
Roff,ShannonR;Sanou,MissaP;Rathore,MobeenH;Levy,JayA;Yamamoto,JanetK
使用来自未经治疗的HIV-1感染长期幸存者（LTS;感染>10年，未接受抗逆转录病毒治疗，ART）、未接受ART的短期HIV-1感染受试者和接受ART治疗的HIV-1感染受试者的外周血单核细胞（PBMC）研究了HIV-1和FIV p24蛋白序列上的交叉反应肽。使用重叠的HIV-1和FIV p24肽对PBMC进行IFNγ-ELISpot和CFSE-增殖分析。通过IFNγ或T细胞增殖分析，超过一半的HIV-1感染受试者（22/31或71%）对一种或多种FIV p24肽池有应答。来自所有3个HIV+组中感染受试者的PBMC和T细胞主要通过IFNγ产生识别一个FIV p24肽库（Fp 14），并通过T细胞增殖分析识别一个额外的FIV p24肽库（Fp 9）。此外，对重叠的SIV p24肽序列的评估鉴定了SIV的Fp 14/Hp 15-对应物Sp14上的保守表位，但在SIV的Fp 9-对应物Sp 9上没有。对这些FIV肽库的响应是高度可重复的，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CD 107 a的表型确定来自Fp 9和Fp 14库的肽表位诱导细胞毒性T淋巴细胞相关分子，包括穿孔素、颗粒酶B、颗粒酶A和/或CD 107 a的表达。被HIV-1感染的患者识别的所选FIV和相应的SIV表位表明这些蛋白质序列在SIV和HIV-1上都是进化保守的（例如，Hp 15：Fp14：Sp14）。这些研究表明，HIV-1、FIV和SIV的免疫原性比较分析可以识别进化保守的T细胞相关慢病毒表位，这些表位可用作预防或免疫治疗的疫苗。
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. IFNγ-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 IFNγ 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 IFNγ 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.