CD8+ T cells from SIV elite controller macaques recognize Mamu-B*08-bound epitopes and select for widespread viral variation.
CD8+ T cells from SIV elite controller macaques recognize Mamu-B*08-bound epitopes and select for widespread viral variation.
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DOI：
10.1371/journal.pone.0001152
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发表时间：
2007-11-14
期刊：
影响因子：
3.7
通讯作者：
Watkins DI
中科院分区：
文献类型：
--
作者：
Loffredo JT;Friedrich TC;León EJ;Stephany JJ;Rodrigues DS;Spencer SP;Bean AT;Beal DR;Burwitz BJ;Rudersdorf RA;Wallace LT;Piaskowski SM;May GE;Sidney J;Gostick E;Wilson NA;Price DA;Kallas EG;Piontkivska H;Hughes AL;Sette A;Watkins DI
人们普遍认为，CD8+ T 细胞反应在控制免疫缺陷病毒复制中发挥着重要作用。 HLA-B27 和-B57 与病毒血症控制的关联支持了这一结论。然而，表达这些等位基因的个体中病毒控制的具体相关性很难确定。我们最近报道，感染猿猴免疫缺陷病毒（SIV）的精英控制者（EC）猕猴体内瞬时 CD8+ 细胞耗竭导致病毒短暂复发。随着 CD8+ 细胞的重新出现，SIV 复制迅速受到控制，这表明这些细胞积极抑制 EC 中的病毒复制。在这里，我们表明该研究中的 3 个 EC 针对受 MHC I 类分子 Mamu-B*08 限制的 Vif、Rev 和 Nef 中的新表位产生了至少 7 种强有力的 CD8+ T 细胞反应。其中两只 Mamu-B*08 阳性动物随后失去了对 SIV 复制的控制。他们的突破性病毒在多个 Mamu-B*08 限制性表位中进行了替换。事实上，我们在一组慢性感染的猕猴中所有新发现的表位中发现了由 Mamu-B*08 限制性 CD8+ T 细胞介导的选择压力的证据。总之，我们的数据表明 Mamu-B*08 限制的 CD8+ T 细胞反应有效控制致病性 SIVmac239 的复制。编码 Mamu-B*08 限制性 CD8+ T 细胞表位的所有七个区域也表现出通常仅在 Mamu-B*08 存在时才能看到的氨基酸替换，这表明我们观察到的变异确实是由 CD8+ T 细胞反应选择的。因此，表达 Mamu-B*08 的印度恒河猴的 SIVmac239 感染可能为了解 CD8+ T 细胞介导的人类 HIV 复制控制提供了一个动物模型。
It is generally accepted that CD8+ T cell responses play an important role in control of immunodeficiency virus replication. The association of HLA-B27 and -B57 with control of viremia supports this conclusion. However, specific correlates of viral control in individuals expressing these alleles have been difficult to define. We recently reported that transient in vivo CD8+ cell depletion in simian immunodeficiency virus (SIV)-infected elite controller (EC) macaques resulted in a brief period of viral recrudescence. SIV replication was rapidly controlled with the reappearance of CD8+ cells, implicating that these cells actively suppress viral replication in ECs. Here we show that three ECs in that study made at least seven robust CD8+ T cell responses directed against novel epitopes in Vif, Rev, and Nef restricted by the MHC class I molecule Mamu-B*08. Two of these Mamu-B*08-positive animals subsequently lost control of SIV replication. Their breakthrough virus harbored substitutions in multiple Mamu-B*08-restricted epitopes. Indeed, we found evidence for selection pressure mediated by Mamu-B*08-restricted CD8+ T cells in all of the newly identified epitopes in a cohort of chronically infected macaques. Together, our data suggest that Mamu-B*08-restricted CD8+ T cell responses effectively control replication of pathogenic SIVmac239. All seven regions encoding Mamu-B*08-restricted CD8+ T cell epitopes also exhibit amino acid replacements typically seen only in the presence of Mamu-B*08, suggesting that the variation we observe is indeed selected by CD8+ T cell responses. SIVmac239 infection of Indian rhesus macaques expressing Mamu-B*08 may therefore provide an animal model for understanding CD8+ T cell-mediated control of HIV replication in humans.
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影响因子：
64.8
作者：
Goulder, PJR;Brander, C;Walker, BD
通讯作者：
Walker, BD
影响因子：
56.9
作者：
Carrington, M;Nelson, GW;O'Brien, SJ
通讯作者：
O'Brien, SJ
DOI：
10.1073/pnas.0408773102
发表时间：
2005-03-22
影响因子：
11.1
作者：
Betts, MR;Exley, B;Ferrari, G
通讯作者：
Ferrari, G
影响因子：
64.8
作者：
Barouch, DH;Kunstman, J;Letvin, NL
通讯作者：
Letvin, NL
影响因子：
82.9
作者：
Evans, DT;O'Connor, DH;Watkins, DI
通讯作者：
Watkins, DI