Later Passages of Neural Progenitor Cells from Neonatal Brain Are More Permissive for Human Cytomegalovirus Infection

Later Passages of Neural Progenitor Cells from Neonatal Brain Are More Permissive for Human Cytomegalovirus Infection
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新生儿大脑神经祖细胞的后期传代更容易感染人类巨细胞病毒

DOI:
10.1128/jvi.01120-13
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发表时间:
2013-07
影响因子:
5.4
通讯作者:
Luo, Min-Hua
Luo, Min-Hua
中科院分区:
医学2区
文献类型:
--
作者:
Schwartz, Philip H.;Britt, William J.;Xu, Jiang;Luo, Min-Hua

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先天性人巨细胞病毒(HCMV)感染是导致出生缺陷最常见的感染性原因,主要是神经系统疾病。神经祖细胞/干细胞(NPCs)是脑室下区的主要细胞类型,易受HCMV感染。在培养中,npc的分化状态可能随着传代而改变,这反过来可能改变对病毒感染的易感性。在此之前,只研究了传代早期(即在传代9之前)的npc,并证明它们对HCMV感染是允许的。在本研究中,对不同胎龄鼻咽癌培养物在体外短代(第3代至第6代)和长代(第11代至第20代)后的生物学和病毒学参数(即细胞形态、鼻咽癌标志物和HCMV受体的表达、病毒进入效率、病毒基因表达、病毒诱导的细胞病变效应和感染性后代的释放)进行了评估。这些参数不受源组织胎龄的显著影响。然而,延长传代培养显示分化开始的证据,增加病毒进入,更有效地生产感染性后代。这些结果证实了NPCs对HCMV感染是完全允许的,延长传代的NPCs启动分化,对HCMV感染更允许。传代较晚的npc分化,更允许HCMV感染,这表明随着大脑发育的推进,胎儿大脑中的HCMV感染可能导致更多的神经细胞丢失,并引起严重的神经功能障碍。
ABSTRACT Congenital human cytomegalovirus (HCMV) infection is the most frequent infectious cause of birth defects, primarily neurological disorders. Neural progenitor/stem cells (NPCs) are the major cell type in the subventricular zone and are susceptible to HCMV infection. In culture, the differentiation status of NPCs may change with passage, which in turn may alter susceptibility to virus infection. Previously, only early-passage (i.e., prior to passage 9) NPCs were studied and shown to be permissive to HCMV infection. In this study, NPC cultures derived at different gestational ages were evaluated after short (passages 3 to 6) and extended (passages 11 to 20) in vitro passages for biological and virological parameters (i.e., cell morphology, expression of NPC markers and HCMV receptors, viral entry efficiency, viral gene expression, virus-induced cytopathic effect, and release of infectious progeny). These parameters were not significantly influenced by the gestational age of the source tissues. However, extended-passage cultures showed evidence of initiation of differentiation, increased viral entry, and more efficient production of infectious progeny. These results confirm that NPCs are fully permissive for HCMV infection and that extended-passage NPCs initiate differentiation and are more permissive for HCMV infection. Later-passage NPCs being differentiated and more permissive for HCMV infection suggest that HCMV infection in fetal brain may cause more neural cell loss and give rise to severe neurological disabilities with advancing brain development.
DOI: 10.1099/0022-1317-71-1-115
发表时间: 1990
期刊: The Journal of general virology
影响因子: --
作者:
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DOI: --
发表时间: 1981
期刊: Perspectives in pediatric pathology
影响因子: --
作者:
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DOI: 10.1128/jvi.42.2.547-557.1982
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影响因子: 5.4
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发表时间: 2002-09-01
影响因子: 6
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通讯作者: Tsutsui, Y
DOI: 10.1016/j.ynpm.2012.06.059
发表时间: 2012
期刊: --
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