Cayota A, Vuillier F, Scott-Algara D, Feuillie V, Dighiero G
Unité d'Immunohématologie et d'Immunopathologie, Paris, France.
Clin Exp Immunol. 1993 Feb;91(2):241-8. doi: 10.1111/j.1365-2249.1993.tb05890.x.
One of the major routes for modulating HIV-1 expression by infected T cells is through the control of transcription initiation from the HIV-1 long terminal repeat (LTR), which is regulated either by its own viral gene products or by several cellular DNA-binding proteins induced during T cell activation. Previous work reported preferential HIV-1 infection and replication of memory CD4 T cells from infected individuals, which was explained either by a higher viral burden of this subset or by differences between naive and memory cells in the activation of the general transcription machinery involved in HIV-1 replication. In this work, we have studied HIV-1 replication by highly purified naive and memory CD4 T cells from asymptomatic seropositive carriers (ASC) and AIDS patients following different activation signals. Our results demonstrate that viral replication in memory cells from ASC was observed after mitogenic (phytohaemagglutinin (PHA) and/or phorbol myristate acetate (PMA)) recombinant tumour necrosis factor-alpha (rTNF-alpha) and CD3-mediated activation. In contrast, in naive subsets, early viral replication was almost exclusively observed upon CD3-mediated activation. AIDS patients are characterized by similar levels of viral replication in both subsets after PHA and soluble or immobilized anti-CD3 MoAb activation. However, naive subsets from AIDS patients still displayed differential requirements since they failed to replicate HIV-1 after treatment with PMA and rTNF-alpha. Taken together, these results provide evidence that HIV-1 replication in CD4+ T cells from infected individuals is a function of the differentiation stage of the cells, the disease stage of the patient and the activation signal employed.
受感染的T细胞调节HIV-1表达的主要途径之一是通过控制HIV-1长末端重复序列（LTR）的转录起始，这一过程由其自身的病毒基因产物或T细胞激活过程中诱导产生的几种细胞DNA结合蛋白调控。此前的研究报道，受感染个体的记忆性CD4 T细胞存在HIV-1的优先感染和复制现象，这一现象的解释要么是该亚群具有更高的病毒载量，要么是初始细胞和记忆细胞在参与HIV-1复制的一般转录机制激活方面存在差异。在本研究中，我们对来自无症状血清阳性携带者（ASC）和艾滋病患者的高度纯化的初始CD4 T细胞和记忆性CD4 T细胞在不同激活信号作用下的HIV-1复制情况进行了研究。我们的结果表明，在丝裂原（植物血凝素（PHA）和/或佛波酯肉豆蔻酸酯乙酸酯（PMA））、重组肿瘤坏死因子-α（rTNF-α）和CD3介导的激活作用下，观察到了ASC记忆细胞中的病毒复制。相比之下，在初始亚群中，早期病毒复制几乎仅在CD3介导的激活作用下被观察到。艾滋病患者的特征是，在PHA和可溶性或固定化抗CD3单克隆抗体激活后，两个亚群中的病毒复制水平相似。然而，艾滋病患者的初始亚群仍表现出不同的需求，因为在用PMA和rTNF-α处理后，它们无法复制HIV-1。综上所述，这些结果证明，受感染个体CD4 + T细胞中的HIV-1复制是细胞分化阶段、患者疾病阶段和所采用激活信号的函数。
