Folks T M, Justement J, Kinter A, Schnittman S, Orenstein J, Poli G, Fauci A S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
J Immunol. 1988 Feb 15;140(4):1117-22.
The present study has investigated the effect of PMA, an inducer of monocyte differentiation, on HIV expression in a chronically infected promonocyte clone. After acute HIV infection of U937 cells, clones that constitutively expressed varying levels of HIV were isolated by limiting dilution. One clone (U1) produced low levels of HIV but was found to increase its production 20-fold after PMA induction, as detected by reverse transcriptase or A capture. Further characterization of U1 indicated that PMA could induce cellular differentiation and maturation in the clone similar to that in uninfected U937 cells. In addition, functional studies revealed that superoxide anion production from the U1 clone was not different from that of uninfected U937 cells. Electron microscopic studies of U1 indicated that PMA induced endocytotic vesicles containing many HIV particles. These studies provide a model at the clonal level to 1) examine latency or chronicity of HIV infection in monocytes and 2) delineate the signals required for conversion to high level viral expression.
本研究调查了单核细胞分化诱导剂佛波酯(PMA)对慢性感染的原单核细胞克隆中HIV表达的影响。U937细胞急性感染HIV后,通过有限稀释法分离出组成性表达不同水平HIV的克隆。一个克隆(U1)产生低水平的HIV,但通过逆转录酶或A捕获检测发现,在PMA诱导后其产量增加了20倍。对U1的进一步表征表明,PMA可诱导该克隆中的细胞分化和成熟,类似于未感染的U937细胞。此外,功能研究表明,U1克隆产生超氧阴离子的情况与未感染的U937细胞无异。对U1的电子显微镜研究表明,PMA诱导了含有许多HIV颗粒的内吞小泡。这些研究在克隆水平上提供了一个模型,用于1)检查HIV在单核细胞中的潜伏或慢性感染情况,以及2)描绘转化为高水平病毒表达所需的信号。