The distribution and kinetics of polyomavirus in lungs of intranasally infected newborn mice
The distribution and kinetics of polyomavirus in lungs of intranasally infected newborn mice
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DOI：
10.1006/viro.1999.0030
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发表时间：
2000-01-05
期刊：
影响因子：
3.7
通讯作者：
Villarreal, LP
中科院分区：
文献类型：
--
作者：
Gottlieb, K;Villarreal, LP
鼻腔感染后维持多瘤病毒(Py)复制的主要细胞类型以及宿主细胞对Py的反应性质尚不清楚。由于这是病毒进入的关键和特殊部位，病毒的基因功能似乎必须适应这些粘膜组织。应用免疫组织化学和原位杂交技术，对新生小鼠鼻内接种Py基因后24 h内肺内支持Py基因表达和复制的细胞类型进行了检测。从感染后第1~10天每天采集肺组织进行Py DNA和早期T抗原分析，并采用保存脆弱的新生儿肺结构的方法进行组织学检查。病毒DNA在支气管腔和细支气管腔内壁的Clara细胞亚群中的数量从2 dpi增加到6dpi，而T抗原表达在支气管腔和细支气管腔的大部分细胞中。在表达T抗原的细胞中观察到一种明显的一过性的增殖模式，从3dpi到6dpi。含Py DNA的细胞脱落到细支气管腔和肺泡管内，但未检测到Py T抗原。在2dpi时最早检测到Py DNA，6dpi后增加，9dpi后突然下降，经原位杂交在肺内未发现病毒DNA的迹象。在出现脱落细胞或Py复制之前，中性粒细胞开始异常渗入，并持续2-3天，随后在8-10 dpi出现淋巴细胞渗入，持续2-3天。MOP1033MT-AS和Rb1 LT-Ag突变体感染Py后，均未见中性粒细胞增殖和中性粒细胞浸润。此外，中性粒细胞的浸润和一过性增生与小鼠腺病毒感染肺部后巨噬细胞的大量浸润形成鲜明对比。因此，Py似乎引起了一种不同的宿主反应模式，这在其他DNA病毒感染中是没有的。(C)2000年学术出版社。
lThe primary cell types that sustain polyomavirus (Py) replication following intranasal infection as well as the nature of the host cellular response to Py were unknown. As this is an essential and specific site for virus entry, it seems likely that viral gene function must be adapted to these mucosal tissues. Using immunohistochemistry and in situ hybridization, we determined the cell types in the lung that support Py gene expression and replication following intranasal inoculation of newborn mice within 24 h of birth. Lungs were collected daily from days 1 to 10 postinfection for Py DNA and early T antigen analysis and for histological examination by H&E staining, using methods that preserve the delicate newborn lung architecture. Viral DNA was present in increasing quantities from 2 to 6 dpi in a subset of the Clara cells lining the inner lumen of the bronchi and bronchioles, while T antigen expression was present in a majority of the cells in the bronchi and bronchiole lumen. A distinct and transient pattern of hyperplasia was observed among the cells expressing T antigen and was present from 3 through 6 dpi. Py DNA-containing cells exfoliated into the bronchiole lumen and alveolar ducts, but Py T antigen was not detected in these cells. Py DNA was first detected at 2 dpi, increased through 6 dpi, and abruptly declined through 9 dpi at which time there was no sign of viral DNA in the lungs by in situ hybridization. An unusual infiltration of neutrophils began before the presence of exfoliated cells or Py replication and continued for 2-3 days and was followed by a lymphocytic infiltration at 8-10 dpi lasting 2-3 days. Neither the hyperplasia nor the neutrophil infiltration occurred following infection with the MOP1033 MT-AS or RB1 LT-Ag mutants of Py. In addition, both the neutrophil infiltration and the transient hyperplasia are in stark contrast to the heavy macrophage infiltration that follows infection of lungs with mouse adenovirus. Thus it appears that Py elicits a distinct host response pattern not seen with other DNA viral infections. (C) 2000 academic Press.