Identification of SIV Nef CD8(+) T cell epitopes restricted by a MHC class I haplotype associated with lower viral loads in a macaque AIDS model.
Identification of SIV Nef CD8(+) T cell epitopes restricted by a MHC class I haplotype associated with lower viral loads in a macaque AIDS model.
复制标题
鉴定受与猕猴艾滋病模型中较低病毒载量相关的 MHC I 类单倍型限制的 SIV Nef CD8( ) T 细胞表位。
DOI：
10.1016/j.bbrc.2014.06.072
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Matano T.
中科院分区：
文献类型：
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作者：
Nomura T;Yamamoto H;Takahashi N;Naruse TK;Kimura A;Matano T.
病毒特异性CD 8 + T细胞应答对于控制人类免疫缺陷病毒（HIV）和猿猴免疫缺陷病毒（SIV）复制至关重要。对HIV感染个体和SIV感染猕猴的多项研究表明，几种主要组织相容性复合体I类（MHC-I）基因型与较低的病毒载量和延迟的AIDS进展有关。了解这些MHC-I基因型的病毒控制机制将有助于制定艾滋病控制的干预策略。我们以前曾报道过恒河猴MHC-I单倍型90-120-Ia与SIVmac 239感染后较低的病毒载量相关。Gag 206 - 216和Gag 241 - 249表位特异性CD 8 + T细胞应答在病毒载量的降低中起重要作用，而Nef特异性CD 8 + T细胞应答在所有90 -120-Ia+猕猴中诱导的对SIV复制的影响尚不清楚。在此，我们鉴定了与90 -120-Ia相关的三个CD 8 + T细胞表位Nef 9 -19、Nef 89 -97和Nef 193 -203。Nef 9 - 19和Nef 193 - 203表位特异性的CD 8 + T细胞应答经常选择突变，导致病毒逃避这些CD 8 +T细胞的识别，表明这些CD 8 +T细胞对SIV复制施加强的抑制压力。结果将有助于阐明与90 -120-Ia相关的病毒控制机制。
Virus-specific CD8+T-cell responses are crucial for the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication. Multiple studies on HIV-infected individuals and SIV-infected macaques have indicated association of several major histocompatibility complex class I (MHC-I) genotypes with lower viral loads and delayed AIDS progression. Understanding of the viral control mechanism associated with these MHC-I genotypes would contribute to the development of intervention strategy for HIV control. We have previously reported a rhesus MHC-I haplotype,90-120-Ia, associated with lower viral loads after SIVmac239 infection. Gag206–216and Gag241–249epitope-specific CD8+T-cell responses have been shown to play a central role in the reduction of viral loads, whereas the effect of Nef-specific CD8+T-cell responses induced in all the90-120-Ia+macaques on SIV replication remains unknown. Here, we identified three CD8+T-cell epitopes, Nef9–19, Nef89–97, and Nef193–203, associated with90-120-Ia. Nef9–19and Nef193–203epitope-specific CD8+T-cell responses frequently selected for mutations resulting in viral escape from recognition by these CD8+T cells, indicating that these CD8+T cells exert strong suppressive pressure on SIV replication. Results would be useful for elucidation of the viral control mechanism associated with90-120-Ia.