Viral evolution in HLA-B27-restricted CTL epitopes in human immunodeficiency virus type 1-infected individuals
Viral evolution in HLA-B27-restricted CTL epitopes in human immunodeficiency virus type 1-infected individuals
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DOI：
10.1099/vir.0.000148
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发表时间：
2015-08-01
影响因子：
3.8
通讯作者：
Kootstra, Neeltje A.
中科院分区：
文献类型：
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作者：
Setiawan, Laurentia C.;Gijsbers, Esther F.;Kootstra, Neeltje A.
HLA-B27 等位基因在人类免疫缺陷病毒 1 型感染的长期非进展者中比例过高。在这些患者中，针对 HLA-B27 限制性病毒表位的强烈 CTL 反应与长期无症状生存相关。事实上，HLA-B27 患者病毒血症的失控与免疫显性 KK10 表位 264 位的 CTL 逃逸有关。病毒 Gag 蛋白中的这种 CTL 逃逸突变与严重的病毒减毒有关，并且可能需要在出现之前存在补偿突变。在这里，我们研究了七名 HLA-B27 阳性患者感染过程中病毒 Gag 蛋白中 HLA-B27 限制性 CTL 表位内的序列进化。获得了在艾滋病诊断前后的不同时间点获得的纵向gag序列，并分析了受HLA-B27限制的表位中是否存在突变，以及潜在的补偿突变。在 HLA-B27 限制性 CTL 表位 IK9 和 DR11 以及免疫显性 KK10 表位中观察到序列变异。然而，在大多数研究的患者中，HLA-B27 限制性 CTL 表位中序列变异的存在与病毒血症的增加无关。此外，我们在整个感染过程中观察到病毒变体的 gag 区域遗传多样性较低，这表明病毒复制较低，并且与 HLA-B27 阳性患者中观察到的低病毒载量相对应。这些数据表明，尽管 HLA-B27 限制性表位中出现病毒突变，但 HLA-B27 阳性患者仍可维持对病毒复制的控制。
The HLA-B27 allele is over-represented among human immunodeficiency virus type 1-infected long-term non-progressors. In these patients, strong CTL responses targeting HLA-B27-restricted viral epitopes have been associated with long-term asymptomatic survival. Indeed, loss of control of viraemia in HLA-B27 patients has been associated with CTL escape at position 264 in the immunodominant KK10 epitope. This CTL escape mutation in the viral Gag protein has been associated with severe viral attenuation and may require the presence of compensatory mutations before emerging. Here, we studied sequence evolution within HLA-B27-restricted CTL epitopes in the viral Gag protein during the course of infection of seven HLA-B27-positive patients. Longitudinal gag sequences obtained at different time points around the time of AIDS diagnosis were obtained and analysed for the presence of mutations in epitopes restricted by HLA-B27, and for potential compensatory mutations. Sequence variations were observed in the HLA-B27-restricted CTL epitopes IK9 and DR11, and the immunodominant KK10 epitope. However, the presence of sequence variations in the HLA-B27-restricted CTL epitopes could not be associated with an increase in viraemia in the majority of the patients studied. Furthermore, we observed low genetic diversity in the gag region of the viral variants throughout the course of infection, which is indicative of low viral replication and corresponds to the low viral load observed in the HLA-B27-positive patients. These data indicated that control of viral replication can be maintained in HLA-B27-positiye patients despite the emergence of viral mutations in HLA-B27-restricted epitopes.