Sinclair J H, Baillie J, Bryant L A, Taylor-Wiedeman J A, Sissons J G
Department of Medicine, University of Cambridge, U.K.
J Gen Virol. 1992 Feb;73 ( Pt 2):433-5. doi: 10.1099/0022-1317-73-2-433.
We have previously shown that a major site of persistence of human cytomegalovirus (HCMV) in healthy carriers is in peripheral blood monocytes. However, monocytes are difficult to infect in vitro with HCMV, and HCMV gene expression cannot be reproducibly detected in peripheral blood cells of healthy carriers. Here we show that the monocytic cell line THP1 is non-permissive for HCMV infection due to a block in expression of the HCMV major immediate early (IE) promoter. This repression is correlated with the presence of a differentiation-specific cellular factor which binds to the imperfect dyad symmetry and the 21 bp enhancer repeats of the major IE promoter regulatory region and which has characteristics of MBF1, a factor which we have previously defined in HCMV non-permissive, undifferentiated teratocarcinoma cells. Both differentiation of THP1 cells into macrophages, which results in a decrease in this factor, or deletion of the factor's binding sites from the IE promoter/enhancer lifts this repression and permits expression from the major IE promoter.
我们之前已经表明，人类巨细胞病毒（HCMV）在健康携带者体内持续存在的一个主要部位是外周血单核细胞。然而，单核细胞在体外很难被HCMV感染，并且在健康携带者的外周血细胞中无法可重复地检测到HCMV基因表达。在此我们表明，单核细胞系THP1对HCMV感染不敏感，这是由于HCMV主要立即早期（IE）启动子的表达受阻。这种抑制与一种分化特异性细胞因子的存在相关，该因子与主要IE启动子调控区域的不完全二元对称和21 bp增强子重复序列结合，并且具有MBF1的特征，MBF1是我们之前在HCMV不敏感的未分化畸胎癌细胞中定义的一种因子。THP1细胞分化为巨噬细胞会导致这种因子减少，或者从IE启动子/增强子中删除该因子的结合位点，都会解除这种抑制，并允许主要IE启动子表达。
