PRODUCTIVE INFECTION OF HUMAN ENDOMETRIAL STROMAL CELLS BY HUMAN CYTOMEGALOVIRUS

PRODUCTIVE INFECTION OF HUMAN ENDOMETRIAL STROMAL CELLS BY HUMAN CYTOMEGALOVIRUS
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DOI:
10.1006/viro.1994.1340
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发表时间:
1994-07-01
期刊:
影响因子:
3.7
通讯作者:
HUANG, ES
HUANG, ES
中科院分区:
医学3区
文献类型:
--
作者:
KOWALIK, TF;YUROCHKO, AD;HUANG, ES

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培养的子宫内膜间质细胞易受生产性人巨细胞病毒(HCMV)感染。子宫内膜间质细胞的感染导致明显的细胞病变效应,包括细胞变圆和聚集,融合,和一些溶解,虽然不是在感染的成纤维细胞中观察到的同步方式。聚集事件使人想起正常子宫内膜间质细胞对周期性雌激素/孕激素水平的反应。免疫荧光分析表明病毒基因产物的表达表明生产性病毒感染。一步生长分析表明,感染性病毒的生产,但滴度是两个对数低于成纤维细胞中获得的,即使HCMV DNA积累到类似的水平,在两种细胞类型。与此相反,病毒DNA复制大大减少子宫内膜间质细胞永生化的温度敏感的SV 40大T基因在允许和非允许的温度。通过北方印迹法对病毒基因表达进行更详细的分析,发现子宫内膜间质细胞中病毒转录本出现较早,初始水平较高。在120 hpi时,在这些细胞中没有观察到HCMV基因表达,即使一半的细胞仍然完整并且细胞基因表达是功能性的。由于这是病毒产生的峰值时间,因此似乎在感染后较晚时间降低病毒基因表达是合理的。是子宫内膜间质细胞中观察到滴度降低的主要原因。这些体外结果加上体内观察与HCMV相关的子宫内膜炎的其他建议,进一步调查HCMV对子宫内膜的影响是必要的。(C)1994年出版社出版。
Cultured endometrial stromal cells were susceptible to productive human cytomegalovirus (HCMV) infection. Infection of endometrial stromal cells resulted in pronounced cytopathic effects including cell rounding and aggregation, fusions, and some lysis, although not in the synchronous fashion observed in infected fibroblasts. The aggregation events were reminiscent of normal endometrial stromal cell responses to cyclical estrogen/progesterone levels. Immunofluorescence analysis demonstrated expression of viral gene products suggesting a productive virus infection. One-step growth analysis showed that infectious virus was produced but the titers were two logs lower than those obtained in fibroblasts even though HCMV DNA accumulated to similar levels in both cell types. In contrast, viral DNA replication was greatly reduced in endometrial stromal cells immortalized with a temperature-sensitive SV40 large T gene at both permissive and nonpermissive temperatures. A more detailed analysis of viral gene expression by Northern blotting revealed earlier appearances and greater initial levels of viral transcripts in endometrial stromal cells. No HCMV gene expression was observed at 120 hpi in these cells even though half of the cells were still intact and cellular gene expression was functional. Since this was the time of peak virus production, it seems plausible that reduced viral gene expression at late times p.i. was a major contributor to the reduced titers observed in endometrial stromal cells. These in vitro results coupled with in vivo observations by others of endometritis associated with HCMV suggest that further investigation into the effects of HCMV on the endometrium is warranted. (C) 1994 Academic Press, Inc.