Porcine reproductive and respiratory syndrome virus (PRRSV) causes apoptosis during its replication in fetal implantation sites
Porcine reproductive and respiratory syndrome virus (PRRSV) causes apoptosis during its replication in fetal implantation sites
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DOI：
10.1016/j.micpath.2011.04.001
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发表时间：
2011-09-01
影响因子：
3.8
通讯作者：
Nauwynck, Hans J.
中科院分区：
文献类型：
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作者：
Karniychuk, Uladzimir U.;Saha, Dipongkor;Nauwynck, Hans J.
由猪繁殖与呼吸综合征病毒（PRRSV）引起的繁殖障碍的特征是晚期流产、早期分娩以及死胎和木乃伊胎和弱仔的增加。PRRS诱导的生殖失败的机制知之甚少。人类妊娠，并发一些病原体导致生殖障碍表现出增加的细胞凋亡在胎膜。由于PRRSV靶细胞存在于健康母猪的子宫内膜/胎儿胎盘中，并且其他器官中的PRRSV感染的巨噬细胞通过凋亡而死亡，因此我们假设PRRSV可以在妊娠的最后阶段在胎儿着床部位复制并诱导凋亡。在本研究中，在胎儿着床部位进行PRRSV阳性和凋亡细胞的鉴定、定位和定量。在妊娠90天时，用10（5）TCID 50 PRRSV 07 V063鼻内接种3只母鼠，并在接种后10天时取样。在妊娠100天处以安乐死的两只未接种母鼠作为对照动物。母鼠接种导致病毒血症，持续至研究结束。在所有接种的母鼠中均检测到经胎盘的PRRSV传播。使用免疫荧光染色，单个PRRSV阳性细胞被发现在子宫内膜结缔组织邻近的PRRSV阳性和阴性胎儿。在PRRSV阳性胎儿的胎盘间充质中，感染细胞更丰富并局部扩散。双重染色显示，所有在胎儿植入部位的PRRSV阳性细胞均为唾液酸粘附素和CD 163阳性。在未接种和接种PRRSV的母鼠的子宫内膜和胎儿胎盘中均检测到凋亡细胞（TUNEL+）。在PRRSV阳性的子宫内膜/胎儿胎盘中凋亡细胞的数量显著较高。PRRSV在感染细胞中引起凋亡，因为20-61%的PRRSV阳性细胞是凋亡的，并且在周围细胞中引起凋亡，因为43-91%的凋亡细胞是病毒阴性的。从本研究中获得的主要结论是，PRRSV在胚胎植入部位复制，并在妊娠后期引起感染的巨噬细胞和周围细胞的凋亡。本文还讨论了猪繁殖与呼吸综合征病毒在胚胎着床部位复制的可能模式以及可能导致生殖障碍的事件。(C)2011爱思唯尔有限公司保留所有权利。
Reproductive failure due to porcine reproductive and respiratory syndrome virus (PRRSV) is characterized by late-term abortions, early farrowing and an increase of dead and mummified fetuses and weak-born piglets. The mechanism of PRRSV-induced reproductive failure is poorly understood. Human pregnancies, complicated by some pathogens leading to reproductive disorders exhibit increased apoptosis in the fetal membranes. Because PRRSV-target cells are present in endometrium/fetal placentas from healthy sows and PRRSV-infected macrophages in other organs die by apoptosis, we hypothesized that PRRSV can replicate and induce apoptosis in the fetal implantation sites at the last stage of gestation. In the present study, identification, localization and quantification of the PRRSV-positive and apoptotic cells were performed in the fetal implantation sites. Three dams were inoculated intranasally with 10(5) TCID50 PRRSV 07V063 at 90 days of gestation and sampled at 10 days post-inoculation. Two non-inoculated dams that were euthanized at 100 days of gestation served as control animals. Inoculation of the dams resulted in a viremia that lasted until the end of the study. Transplacental PRRSV spread was detected in all inoculated dams. Using immunofluorescence staining, single PRRSV-positive cells were found in the endometrial connective tissues adjacent to both PRRSV-positive and PRRSV-negative fetuses. In the fetal placental mesenchyme of the PRRSV-positive fetuses, infected cells were more abundant and spread focally. Double staining showed that all PRRSV-positive cells in the fetal implantation sites were positive for sialoadhesin and CD163. Apoptotic cells (TUNEL+) were detected in endometrium and fetal placentas of both non- and PRRSV-inoculated dams. The number of apoptotic cells was significantly higher in PRRSV-positive endometrium/fetal placentas. PRRSV caused apoptosis in infected cells since 20-61% of PRRSV-positive cells were apoptotic and in surrounding cells since 43-91% of the apoptotic cells were virus-negative. The main conclusion obtained from the present study is that PRRSV replicates in the fetal implantation sites and causes apoptosis in infected macrophages and surrounding cells at the last stage of gestation. The possible mode of PRRSV replication in the fetal implantation sites and the events that might contribute to the reproductive disorders are discussed. (C) 2011 Elsevier Ltd. All rights reserved.