HLA Class I-Mediated HIV-1 Control in Vietnamese Infected with HIV-1 Subtype A/E
HLA Class I-Mediated HIV-1 Control in Vietnamese Infected with HIV-1 Subtype A/E
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DOI：
10.1128/jvi.01749-17
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发表时间：
2018-03-01
影响因子：
5.4
通讯作者：
Takiguchi, Masafumi
中科院分区：
文献类型：
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作者：
Chikata, Takayuki;Giang Van Tran;Takiguchi, Masafumi
HIV-1 特异性细胞毒性 T 细胞 (CTL) 在控制 HIV-1 B 或 C 亚型感染中发挥着重要作用。然而，CTL 在 HIV-1 A/E 亚型感染中的作用仍不清楚。在这里，我们研究了 HLA I 类等位基因与感染 A/E 亚型病毒的未接受治疗的越南人临床结果的关联。我们发现 HLA-C*12:02 与较低的血浆病毒载量 (pVL) 和较高的 CD4 计数显着相关，并且与没有这些各自基因型的个体相比，HLA-A*29:01-B*07:05-C*15:05 单倍型与较高的 pVL 和较低的 CD4 计数显着相关。 9 个 Pol 突变和 3 个 Nef 突变与 HLA-A*29:01-B*07:05C*15:05 单倍型中的至少一个 HLA 等位基因相关，HLA 相关 Pol 突变数量与 CD4 计数之间呈强负相关，与具有这些 HLA 等位基因的个体的 pVL 呈正相关。结果表明，受这些 HLA 等位基因限制的 CTL 选择的突变积累会影响 HIV 控制。 重要性 以往大多数关于 HLA 与 HIV-1 感染后疾病进展关联的研究都是在感染 HIV-1 亚型 B 和 C 的人群中进行的，而针对感染亚洲 A/E 亚型病毒的人群进行的此类基于人群的研究却很少报道。在这项研究中，我们分析了 536 名 HIV-1 A/E 亚型感染越南人的 HLA I 类等位基因与临床结果的关联。我们发现 HLA-C*12:02 具有保护性，而 HLA 单倍型 HLA-A*29:01-B*07:05-C*15:05 是有害的。与没有突变的个体相比，携带与有害 HLA 单倍型中至少一种 HLA 等位基因相关的 HIV-1 突变的个体具有更高的血浆病毒载量和更低的 CD4 计数，这表明病毒适应并逃离了 HLA 介导的免疫控制。本研究确定了 HIV-1 A/E 亚型感染的保护性等位基因和有害单倍型，这与 HIV-1 B 和 C 亚型感染人群的保护性等位基因和有害单倍型不同。
HIV-1-specific cytotoxic T cells (CTLs) play an important role in the control of HIV-1 subtype B or C infection. However, the role of CTLs in HIV-1 subtype A/E infection still remains unclear. Here we investigated the association of HLA class I alleles with clinical outcomes in treatment-naive Vietnamese infected with subtype A/E virus. We found that HLA-C*12:02 was significantly associated with lower plasma viral loads (pVL) and higher CD4 counts and that the HLA-A*29:01-B*07:05-C*15:05 haplotype was significantly associated with higher pVL and lower CD4 counts than those for individuals without these respective genotypes. Nine Pol and three Nef mutations were associated with at least one HLA allele in the HLA-A*29:01-B*07:05C*15:05 haplotype, with a strong negative correlation between the number of HLA-associated Pol mutations and CD4 count as well as a positive correlation with pVL for individuals with these HLA alleles. The results suggest that the accumulation of mutations selected by CTLs restricted by these HLA alleles affects HIV control.IMPORTANCE Most previous studies on HLA association with disease progression after HIV-1 infection have been performed on cohorts infected with HIV-1 subtypes B and C, whereas few such population-based studies have been reported for cohorts infected with the Asian subtype A/E virus. In this study, we analyzed the association of HLA class I alleles with clinical outcomes for 536 HIV-1 subtype A/E-infected Vietnamese individuals. We found that HLA-C*12:02 is protective, while the HLA haplotype HLA-A*29:01-B*07:05-C*15:05 is deleterious. The individuals with HIV-1 mutations associated with at least one of the HLA alleles in the deleterious HLA haplotype had higher plasma viral loads and lower CD4 counts than those of individuals without the mutations, suggesting that viral adaptation and escape from HLA-mediated immune control occurred. The present study identifies a protective allele and a deleterious haplotype for HIV-1 subtype A/E infection which are different from those identified for cohorts infected with HIV-1 subtypes B and C.