Gammaherpesvirus infection modulates the temporal and spatial expression of SCGB1A1 (CCSP) and BPIFA1 (SPLUNC1) in the respiratory tract.

Gammaherpesvirus infection modulates the temporal and spatial expression of SCGB1A1 (CCSP) and BPIFA1 (SPLUNC1) in the respiratory tract.
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DOI:
10.1038/labinvest.2014.162
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发表时间:
2015-06
影响因子:
5
通讯作者:
Stewart, James P.
Stewart, James P.
中科院分区:
医学2区
文献类型:
--
作者:
Leeming, Gail H.;Kipar, Anja;Hughes, David J.;Bingle, Lynne;Bennett, Elaine;Moyo, Nathifa A.;Tripp, Ralph A.;Bigley, Alison L.;Bingle, Colin D.;Sample, Jeffery T.;Stewart, James P.

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小鼠γ-疱疹病毒68(MHV-68)感染小鼠来源的小鼠品系是一种已建立的γ-疱疹病毒感染模型。我们以前已经开发了一种替代系统,使用天然宿主,森林鼠(黑线姬鼠),并显示MHV-68 M3趋化因子结合蛋白显着有助于MHV-68的发病机制。在这里,我们展示了A。使用高密度微阵列对林化螨进行的研究表明,M3影响参与宿主反应的基因的表达,包括编码分泌到呼吸道中的潜在先天防御蛋白的Scgb 1a 1和Bpifa 1。对MHV-68感染动物的进一步分析显示,SCGB 1A 1和BPIFA 1的蛋白质和RNA水平在感染后第7天(p.i.)但在感染后第14天增加。与M3缺陷和模拟感染的动物相比。表达的调节在细支气管中最明显,但也存在于支气管和气管中。使用RNA原位杂交和免疫组织学的双重染色表明,大部分BPIFA 1表达与SCGB 1A 1一起沿着发生在俱乐部细胞中,并且BPIFA 1储存在这些细胞中的颗粒内。在感染后第14天,SCGB 1A 1和BPIFA 1表达的增加与对照组相比无显著性差异。与俱乐部细胞分化为粘液分泌细胞有关。我们的数据强调了俱乐部细胞的作用以及SCGB 1A 1和BPFA 1在呼吸道病毒感染期间作为先天防御介质的潜力。
Murine γ-herpesvirus 68 (MHV-68) infection of Mus musculus-derived strains of mice is an established model of γ-herpesvirus infection. We have previously developed an alternative system using a natural host, the wood mouse (Apodemus sylvaticus), and shown that the MHV-68 M3 chemokine-binding protein contributes significantly to MHV-68 pathogenesis. Here we demonstrate in A. sylvaticus using high-density micro-arrays that M3 influences the expression of genes involved in the host response including Scgb1a1 and Bpifa1 that encode potential innate defense proteins secreted into the respiratory tract. Further analysis of MHV-68-infected animals showed that the levels of both protein and RNA for SCGB1A1 and BPIFA1 were decreased at day 7 post infection (p.i.) but increased at day 14 p.i. as compared with M3-deficient and mock-infected animals. The modulation of expression was most pronounced in bronchioles but was also present in the bronchi and trachea. Double staining using RNA in situ hybridization and immunohistology demonstrated that much of the BPIFA1 expression occurs in club cells along with SCGB1A1 and that BPIFA1 is stored within granules in these cells. The increase in SCGB1A1 and BPIFA1 expression at day 14 p.i. was associated with the differentiation of club cells into mucus-secreting cells. Our data highlight the role of club cells and the potential of SCGB1A1 and BPIFA1 as innate defense mediators during respiratory virus infection.
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发表时间: 2005-03-01
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发表时间: 1990-06-01
影响因子: 3.8
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EFSTATHIOU, S;HO, YM;MINSON, AC
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发表时间: 2002-11-18
影响因子: 15.3
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作者:
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