Department of Pediatrics, Northwestern University Feinberg School of Medicine and Children's Memorial Hospital, Chicago, Illinois 60614, USA.
J Med Virol. 2011 Jan;83(1):24-32. doi: 10.1002/jmv.21933.
Suppression of human immunodeficiency virus (HIV) replication by CD8+ T-cells (CD8 suppression) contributes to survival in adults and children <1 year. Soluble CD8 suppression can also be seen in some older children with AIDS. The factor responsible, CD8-derived antiviral factor (CAF), acts at the level of HIV RNA transcription. Differential gene expression techniques have been used to define the gene(s) mediating this phenomenon in adults. Recently, CAF has been linked to exosomes secreted by CD8+ T-cells. To compare the gene expression profiles from pediatric patients with each other, with those reported in 2 previous studies in adults and in those reportedly related to exosomes, we used differential gene expression to study three older children with HIV infection, one who did demonstrate soluble CD-8 suppression and two who did not. Eighteen differentially expressed genes were also seen in one adult study (P = 0.002, χ(2) test), and 38 such genes (P < 0.0001, χ(2) test) in a second adult study. In addition, two exosome components and some RNA's related to exosomal proteins were also differentially expressed. In children with HIV infection, we found significant differentially expressed genes that correlated to those previously reported in two studies in adults. Our data also lends some support to the recent identification of CAF with exosomes secreted by CD8+ T-cells.
CD8+ T 细胞(CD8 抑制)对人类免疫缺陷病毒 (HIV) 复制的抑制作用有助于成人和 <1 岁的儿童的存活。一些患有艾滋病的大龄儿童也可出现可溶性 CD8 抑制。负责这一现象的因子是 CD8 衍生的抗病毒因子 (CAF),其作用于 HIV RNA 转录水平。采用差异基因表达技术来定义成人中介导这一现象的基因。最近,CAF 与 CD8+ T 细胞分泌的外体有关。为了将儿科患者的基因表达谱彼此进行比较,以及与之前在成人中进行的两项研究和与外体相关的报道进行比较,我们使用差异基因表达技术研究了 3 名 HIV 感染的大龄儿童,其中 1 名显示可溶性 CD8 抑制,另外 2 名没有。在一项成人研究中还观察到 18 个差异表达基因(P = 0.002,卡方检验),在第二项成人研究中观察到 38 个差异表达基因(P < 0.0001,卡方检验)。此外,两个外体成分和一些与外体蛋白相关的 RNA 也表现出差异表达。在 HIV 感染的儿童中,我们发现了与之前在两项成人研究中报道的显著差异表达基因相关的基因。我们的数据还为最近确定的与 CD8+ T 细胞分泌的外体有关的 CAF 提供了一些支持。