Murine Cytomegalovirus Glycoprotein O Promotes Epithelial Cell Infection In Vivo
Murine Cytomegalovirus Glycoprotein O Promotes Epithelial Cell Infection In Vivo
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鼠巨细胞病毒糖蛋白O促进体内上皮细胞感染
DOI：
10.1128/jvi.01378-18
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发表时间：
2019
影响因子：
5.4
通讯作者：
Stevenson
中科院分区：
文献类型：
--
作者：
Yunis J;Farrell;Lawler;Davis-Poynter;Brizić;Jonjić;Stevenson
巨细胞病毒(CMV)跨不同类型的细胞建立全身性感染。改变嗜性的糖蛋白可能会引导它们的传播。糖蛋白O(GO)是人巨细胞病毒(HCMV)和小鼠巨细胞病毒(MCMV)的非必需融合复合体成分。我们测试了它对MCMV从呼吸道传播的贡献。在体外，MCMV缺乏GO弱感染的成纤维细胞和上皮细胞。细胞结合完好，但穿透延迟。相比之下，髓系感染被保存下来，在以髓系和2型肺泡上皮细胞为主要病毒靶点的肺部，缺乏GO的MCMV显示出明显的髓系感染偏好。其较差的上皮细胞感染与较差的原代病毒产量和降低的毒力有关。全身性传播是通过感染的CD11c+髓系细胞进行的，最初是完整的，但后来减少了，因为较少的上皮感染最终导致较少的髓系感染。因此，外周和全身MCMV感染之间的紧密联系使GO依赖感染在宿主定植中发挥核心作用。这反映出其系统性扩散的能力。需要一种疫苗，但最好的病毒靶点尚不清楚。人们的注意力集中在病毒粒子膜融合复合体上。它有两种形式，所以我们需要知道每种形式对宿主殖民的贡献。一种是病毒粒子糖蛋白O。我们使用小鼠巨细胞病毒，它有相当的融合复合体，来确定糖蛋白O在粘膜感染后的重要性。我们发现，它可以驱动上皮细胞中的局部病毒复制。它不需要感染髓系细胞，从而建立全身感染，但糟糕的局部复制减少了作为次要效应的全身传播。因此，靶向人巨细胞病毒糖蛋白O具有减少局部和全身感染的潜力。
Cytomegaloviruses (CMVs) establish systemic infections across diverse cell types. Glycoproteins that alter tropism can potentially guide their spread. Glycoprotein O (gO) is a nonessential fusion complex component of both human CMV (HCMV) and murine CMV (MCMV). We tested its contribution to MCMV spread from the respiratory tract.In vitro, MCMV lacking gO poorly infected fibroblasts and epithelial cells. Cell binding was intact, but penetration was delayed. In contrast, myeloid infection was preserved, and in the lungs, where myeloid and type 2 alveolar epithelial cells are the main viral targets, MCMV lacking gO showed a marked preference for myeloid infection. Its poor epithelial cell infection was associated with poor primary virus production and reduced virulence. Systemic spread, which proceeds via infected CD11c+myeloid cells, was initially intact but then diminished, because less epithelial infection led ultimately to less myeloid infection. Thus, the tight linkage between peripheral and systemic MCMV infections gave gO-dependent infection a central role in host colonization.IMPORTANCEHuman cytomegalovirus is a leading cause of congenital disease. This reflects its capacity for systemic spread. A vaccine is needed, but the best viral targets are unclear. Attention has focused on the virion membrane fusion complex. It has 2 forms, so we need to know what each contributes to host colonization. One includes the virion glycoprotein O. We used murine cytomegalovirus, which has equivalent fusion complexes, to determine the importance of glycoprotein O after mucosal infection. We show that it drives local virus replication in epithelial cells. It was not required to infect myeloid cells, which establish systemic infection, but poor local replication reduced systemic spread as a secondary effect. Therefore, targeting glycoprotein O of human cytomegalovirus has the potential to reduce both local and systemic infections.
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影响因子：
5.4
作者：
Paul T. Wille;A. J. Knoche;J. Nelson;M. Jarvis;David C. Johnson
通讯作者：
Paul T. Wille;A. J. Knoche;J. Nelson;M. Jarvis;David C. Johnson
鼠巨细胞病毒的病毒趋化因子MCK-2作为GH/GL/MCK-2复合物的一部分促进感染。
影响因子：
6.7
作者：
Wagner FM;Brizic I;Prager A;Trsan T;Arapovic M;Lemmermann NA;Podlech J;Reddehase MJ;Lemnitzer F;Bosse JB;Gimpfl M;Marcinowski L;MacDonald M;Adler H;Koszinowski UH;Adler B
通讯作者：
Adler B
影响因子：
8.8
作者：
Pass, Robert F.
通讯作者：
Pass, Robert F.
鼠巨细胞病毒 M73.5 基因是 3 共端可变剪接基因家族的成员，编码 gp24 病毒体糖蛋白。
影响因子：
3.7
作者：
A. Scalzo;P. Dallas;C. Forbes;A. Mikosza;P. Fleming;L. Lathbury;P. Lyons;S. Laferté;M. Craggs;L. Loh
通讯作者：
L. Loh
DOI：
10.1099/vir.0.005785-0
发表时间：
2009-03
期刊：
The Journal of general virology
影响因子：
--
作者：
Gillet L;May JS;Stevenson PG
通讯作者：
Stevenson PG