Geleziunas R, Bour S, Wainberg M A
McGill AIDS Centre, Lady Davis Institute-Jewish General Hospital, Montreal, Quebec, Canada.
J Leukoc Biol. 1994 May;55(5):589-95. doi: 10.1002/jlb.55.5.589.
We previously demonstrated that chronic infection of a monocytic cell line (U-937) with human immunodeficiency virus type 1 (HIV-1) was not accompanied by down-modulation of CD4 transcription, unlike the situation with CD4+ T lymphocyte lines. To better understand the refractoriness of monocytes to alterations in levels of CD4 mRNA, we treated HIV-IIIB chronically infected U-937 cells with phorbol myristate acetate (PMA), a known stimulus of HIV gene expression. Although PMA caused a significant increase in HIV mRNA levels that was sustained over 7 days, no effect on CD4 transcript levels was noted. Clonal derivatives of HIV-IIIB-infected U-937 cells, which produced a variety of infectious and defective particles, were likewise not affected in ability to produce CD4 mRNA. To rule out the possibility that U-937 cells select out HIV-1 variants unable to modulate CD4 mRNA levels, we passaged infectious virus from a U-937 clonal derivative (UHC1) onto different monocytic and T lymphocytic cell lines. In monocytic cell lines (U-937, PLB-985, THP-1), we observed an avirulent infection that did not affect CD4 mRNA levels, whereas UHC1 infection of each of two T lymphocytic cell lines (CEM-T4, Jurkat) caused both cytopathic replication and reductions in CD4 mRNA levels. In one case (Jurkat), variants expressing low CD4 mRNA may have emerged, because the outgrowth no longer expressed viral products. In the other case (CEM-T4), high expression of viral genes was accompanied by CD4 mRNA down-modulation, suggesting either that low-CD4-expressing variants were selected that maintained viral gene expression or that CD4 gene expression was repressed by viral products.
我们之前证明，与CD4+ T淋巴细胞系的情况不同，用1型人类免疫缺陷病毒（HIV-1）对单核细胞系（U-937）进行慢性感染时，CD4转录不会下调。为了更好地理解单核细胞对CD4 mRNA水平变化的难治性，我们用佛波酯肉豆蔻酸酯乙酸酯（PMA）处理慢性感染HIV-IIIB的U-937细胞，PMA是一种已知的HIV基因表达刺激物。尽管PMA使HIV mRNA水平显著增加并持续7天，但未观察到对CD4转录本水平有影响。感染HIV-IIIB的U-937细胞的克隆衍生物产生了各种感染性和缺陷性颗粒，其产生CD4 mRNA的能力同样未受影响。为了排除U-937细胞选择出无法调节CD4 mRNA水平的HIV-1变体的可能性，我们将来自U-937克隆衍生物（UHC1）的感染性病毒接种到不同的单核细胞系和T淋巴细胞系上。在单核细胞系（U-937、PLB-985、THP-1）中，我们观察到一种无毒感染，未影响CD4 mRNA水平，而UHC1对两种T淋巴细胞系（CEM-T4、Jurkat）中的每一种进行感染均导致细胞病变性复制和CD4 mRNA水平降低。在一种情况（Jurkat）下，可能出现了表达低水平CD4 mRNA的变体，因为其生长不再表达病毒产物。在另一种情况（CEM-T4）下，病毒基因的高表达伴随着CD4 mRNA下调，这表明要么选择了维持病毒基因表达的低CD4表达变体，要么CD4基因表达被病毒产物抑制。
