Hierarchy of multiple viral CD8+ T-cell epitope mutations in sequential selection in simian immunodeficiency infection
Hierarchy of multiple viral CD8+ T-cell epitope mutations in sequential selection in simian immunodeficiency infection
复制标题
猿猴免疫缺陷感染序贯选择中多个病毒 CD8 T 细胞表位突变的层次结构
DOI：
10.1016/j.bbrc.2022.03.108
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发表时间：
2022
影响因子：
3.1
通讯作者：
Nomura Takushi
中科院分区：
文献类型：
--
作者：
Ntim Nana Afia Asante;Ishii Hiroshi;Jomori Moe;Yamamoto Hiroyuki;Matano Tetsuro;Nomura Takushi
CD 8 + T细胞反应对病毒复制产生强大的抑制压力，并选择HIV感染中的病毒逃逸突变。由主要组织相容性复合物I类（MHC-I）限制的多个病毒表位被CD 8 +T细胞靶向。在单个表位编码区中病毒逃逸突变的顺序选择可能导致基于CD 8 +T细胞的病毒控制失败，从而导致疾病进展。然而，这种表位突变的顺序选择如何发生尚未完全确定。在这里，我们研究了在猴免疫缺陷病毒mac 239（SIVmac 239）感染的猕猴艾滋病模型中7个CD 8 + T细胞表位编码区的病毒突变的顺序选择。在7只感染SIVmac 239的缅甸恒河猴中，在感染后一年内，在7个90 - 120-Ia相关的CD 8 + T细胞表位编码区中的5 - 7个中观察到了MHC-I单倍型90 - 120-Ia的病毒突变选择。在7个CD 8 + T细胞表位中，首先在Gag 206 - 216和Nef 9 -19两个表位检测到病毒的突变选择，最后在大多数动物中在Vif 114 - 124表位检测到病毒的突变选择。6个月内的病毒载量与感染后1年突变的CD 8 + T细胞表位编码区的数量显著相关。四聚体分析揭示了Gag 241 - 249特异性CD 8 + T细胞应答的早期诱导，这并不总是导致Gag 241 - 249表位中病毒突变的早期选择，这表明表位突变选择的顺序可能不仅仅由免疫显性决定。这种使用90 -120-Ia阳性猕猴的SIV感染模型将有助于分析顺序表位突变选择的决定因素，有助于我们理解HIV感染中病毒-宿主CD 8 + T细胞相互作用。
CD8+T-cell responses exert strong suppressive pressure on viral replication and select for viral escape mutations in HIV infection. Multiple viral epitopes restricted by major histocompatibility complex class I (MHC-I) are targeted by CD8+T cells. Sequential selection of viral escape mutations in individual epitope-coding regions could result in failure in CD8+T cell-based viral control leading to disease progression. However, how this sequential selection of epitope mutations occurs has not fully been determined. Here, we examined sequential selection of viral mutations in seven CD8+T-cell epitope-coding regions in a macaque AIDS model of simian immunodeficiency virus mac239 (SIVmac239) infection. In seven SIVmac239-infected Burmese rhesus macaques possessing MHC-I haplotype90-120-Ia, selection of viral mutations was observed in five to seven of the seven90-120-Ia-associated CD8+T-cell epitope-coding regions in a year post-infection. Of the seven CD8+T-cell epitopes, viral mutation selection was detected first at two epitopes, Gag206-216and Nef9-19, but was found finally at Vif114-124epitope in most animals. Viral loads in 6 months were significantly associated with the number of mutated CD8+T-cell epitope-coding regions 1 year post-infection. Tetramer analysis revealed early induction of Gag241-249specific CD8+T-cell responses, which did not always result in early selection of viral mutations in the Gag241-249epitope, suggesting that the order of epitope mutation selection may not be determined only by immunodominance. This SIV infection model using90-120-Ia-positive macaques would be useful for analysis of the determinants for sequential epitope mutation selection, contributing to our understanding of virus-host CD8+T-cell interaction in HIV infection.