Factors Associated With the Control of Viral Replication and Virologic Breakthrough in a Recently Infected HIV-1 Controller.
Factors Associated With the Control of Viral Replication and Virologic Breakthrough in a Recently Infected HIV-1 Controller.
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DOI：
10.1016/j.ebiom.2017.01.034
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发表时间：
2017-02
期刊：
影响因子：
11.1
通讯作者：
Blankson JN
中科院分区：
文献类型：
--
作者：
Walker-Sperling VE;Pohlmeyer CW;Veenhuis RT;May M;Luna KA;Kirkpatrick AR;Laeyendecker O;Cox AL;Carrington M;Bailey JR;Arduino RC;Blankson JN
HIV-1控制者是指在没有抗逆转录病毒治疗的情况下控制HIV-1病毒复制的患者。在感染过程的早期就实现了控制，但限制病毒复制的机制尚不完全清楚。我们描述了一个急性HIV-1感染的患者，发现HIV-1 RNA水平< 100拷贝/mL。她没有任何已知的保护性HLA等位基因，但存在CD8 + T细胞和自然杀伤（NK）细胞的显著免疫激活，两种细胞类型都抑制病毒复制。从这个病人身上培养出来的病毒在体外复制的能力和从她的伴侣身上分离出来的病毒一样好，她的伴侣是一名艾滋病患者，也是传播源。病毒学突破发生在她初次就诊9个月后，并与CD4 + T细胞激活水平的增加和NK细胞抑制能力的显著下降有关。值得注意的是，CD8 + T细胞抑制能力得以保留，靶向Gag表位没有新的逃逸突变。这些发现表明，在一些没有保护性HLA等位基因的急性HIV-1感染患者中，完全复制能力的病毒可以被控制，NK细胞反应可能有助于这种病毒复制的早期控制。我们发现HIV-1控制者感染了致病性病毒，但在初次感染期间保持了低病毒载量。她激活了NK细胞和CD8+ T细胞，两种细胞在感染后不久抑制了HIV-1的复制。她最终失去了对病毒复制的控制，这与NK细胞抑制活性的降低有关。HIV-1控制者是指不使用HIV-1药物就能控制病毒的患者。这些病人可能会告诉我们如何设计一种针对HIV-1的疫苗。对于如何在这些患者感染的早期阶段控制病毒，人们知之甚少。在这里，我们显示最近感染的HIV-1控制者对病毒有很强的自然杀伤细胞反应。有趣的是，9个月后，她失去了对病毒的控制，她对病毒的自然杀伤细胞反应减弱了。我们的研究表明，自然杀伤细胞可能有助于在感染的早期阶段控制病毒。
HIV-1 controllers are patients who control HIV-1 viral replication without antiretroviral therapy. Control is achieved very early in the course of infection, but the mechanisms through which viral replication is restricted are not fully understood. We describe a patient who presented with acute HIV-1 infection and was found to have an HIV-1 RNA level of < 100 copies/mL. She did not have any known protective HLA alleles, but significant immune activation of CD8 + T cells and natural killer (NK) cells was present, and both cell types inhibited viral replication. Virus cultured from this patient replicated as well in vitro as virus isolated from her partner, a patient with AIDS who was the source of transmission. Virologic breakthrough occurred 9 months after her initial presentation and was associated with an increase in CD4 + T cell activation levels and a significant decrease in NK cell inhibitory capacity. Remarkably, CD8 + T cell inhibitory capacity was preserved and there were no new escape mutations in targeted Gag epitopes. These findings suggest that fully replication-competent virus can be controlled in acute HIV-1 infection in some patients without protective HLA alleles and that NK cell responses may contribute to this early control of viral replication. We show that an HIV-1 controller was infected with pathogenic virus yet maintained low viral loads during primary infection. She had activated NK cells and CD8+ T cells and both cell types suppressed HIV-1 replication shortly after infection. She eventually lost control of viral replication, and this was associated with a reduction in NK cell suppressive activity. HIV-1 controllers are patients who control the virus without HIV-1 medications. These patients may teach us how to design a vaccine against HIV-1. Little is known about how the virus is controlled in the early phase of infection in these patients. Here we show that a recently infected HIV-1 controller had a strong natural killer cell response to the virus. Interestingly, she lost control of the virus 9 months later and her natural killer cell response to the virus was diminished. Our work suggests that natural killer cells may have contributed to viral control in the early phase of infection.