Permissive human cytomegalovirus infection of a first trimester extravillous cytotrophoblast cell line.

Permissive human cytomegalovirus infection of a first trimester extravillous cytotrophoblast cell line.
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DOI:
10.1186/1743-422x-1-8
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发表时间:
2004-11-17
期刊:
影响因子:
4.8
通讯作者:
Morris CA
Morris CA
中科院分区:
医学3区
文献类型:
--
作者:
LaMarca HL;Sainz B Jr;Morris CA

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人类巨细胞病毒 (HCMV) 是美国和欧洲先天性病毒感染的主要原因。尽管与产前 HCMV 感染相关的发病率很高,但人们对该病毒如何在怀孕期间感染胎儿知之甚少。迄今为止,原代人细胞滋养层 (CTB) 已被用于研究胎盘 HCMV 感染和复制;然而,这些细胞的最小有丝分裂潜力将实验限制在几天内,这对于缓慢复制病毒的机制研究可能是有问题的。本研究的目的是确定人类妊娠早期 CTB 细胞系 SGHPL-4 是否允许 HCMV 感染,从而克服这些限制。早在 SGHPL-4 细胞感染后 3 小时就检测到 HCMV 立即早期 (IE) 蛋白表达,并随着时间的推移逐渐增加。 HCMV 生长测定显示细胞裂解物和培养物上清液中都存在感染性病毒,表明发生了病毒复制和子代病毒的释放。与人类成纤维细胞相比,CTB 中的病毒复制延迟,这与之前报告的 HCMV 感染的原发性 CTB 中病毒动力学延迟的研究一致。这些结果表明 SGHPL-4 细胞完全允许完整的 HCMV 复制周期。我们的研究结果表明,这些细胞可能作为未来妊娠早期 HCMV 发病机制研究的有用工具。
Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection in the United States and Europe. Despite the significant morbidity associated with prenatal HCMV infection, little is known about how the virus infects the fetus during pregnancy. To date, primary human cytotrophoblasts (CTBs) have been utilized to study placental HCMV infection and replication; however, the minimal mitotic potential of these cells restricts experimentation to a few days, which may be problematic for mechanistic studies of the slow-replicating virus. The aim of this study was to determine whether the human first trimester CTB cell line SGHPL-4 was permissive for HCMV infection and therefore could overcome such limitations. HCMV immediate early (IE) protein expression was detected as early as 3 hours post-infection in SGHPL-4 cells and progressively increased as a function of time. HCMV growth assays revealed the presence of infectious virus in both cell lysates and culture supernatants, indicating that viral replication and the release of progeny virus occurred. Compared to human fibroblasts, viral replication was delayed in CTBs, consistent with previous studies reporting delayed viral kinetics in HCMV-infected primary CTBs. These results indicate that SGHPL-4 cells are fully permissive for the complete HCMV replicative cycle. Our findings suggest that these cells may serve as useful tools for future mechanistic studies of HCMV pathogenesis during early pregnancy.