LaMarca Heather L, Sainz Bruno, Morris Cindy A
Interdisciplinary Program in Molecular and Cellular Biology, Tulane University Health Sciences Center, New Orleans, LA, USA.
Virol J. 2004 Nov 17;1:8. doi: 10.1186/1743-422X-1-8.
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.
人巨细胞病毒（HCMV）是美国和欧洲先天性病毒感染的主要原因。尽管产前HCMV感染会导致严重的发病情况，但对于该病毒在孕期如何感染胎儿却知之甚少。迄今为止，原代人细胞滋养层细胞（CTB）已被用于研究胎盘HCMV感染和复制；然而，这些细胞极低的有丝分裂潜能将实验限制在几天内，这对于研究这种复制缓慢的病毒的机制研究可能存在问题。本研究的目的是确定人孕早期CTB细胞系SGHPL-4是否允许HCMV感染，从而能否克服此类限制。在SGHPL-4细胞中，早在感染后3小时就检测到HCMV立即早期（IE）蛋白表达，并且随着时间的推移逐渐增加。HCMV生长试验表明，在细胞裂解物和培养上清液中均存在感染性病毒，这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中的病毒复制有所延迟，这与先前报道HCMV感染原代CTB时病毒动力学延迟的研究结果一致。这些结果表明，SGHPL-4细胞完全允许HCMV进行完整的复制周期。我们的研究结果表明，这些细胞可能成为未来早期妊娠期间HCMV发病机制机制研究的有用工具。
