Rhadinovirus host entry by co-operative infection.
Rhadinovirus host entry by co-operative infection.
复制标题
DOI：
10.1371/journal.ppat.1004761
复制
发表时间：
2015-03
期刊：
影响因子：
6.7
通讯作者：
Stevenson PG
中科院分区：
文献类型：
--
作者：
Lawler C;Milho R;May JS;Stevenson PG
横纹肌病毒建立了具有临床和经济重要性的慢性感染。有几种表现为呼吸道传播并引起肺部病变。我们使用Murid Herpesvirus-4 （MuHV-4）来了解rhadinovirus肺部感染是如何发生的。原发性上皮细胞或B细胞感染常被认为。MuHV-4靶向肺泡巨噬细胞，它们的消耗显著减少了宿主的进入。虽然进入宿主是有效的，但肺泡巨噬细胞缺乏肝素-一种重要的腺病毒结合靶点-并且在体外感染较差。原位分析显示，病毒粒子最初不是与巨噬细胞结合，而是与肝素+ 1型肺泡上皮细胞（AECs）结合。尽管上皮细胞系在体外很容易内吞MuHV-4，但aec却没有。巨噬细胞获得非结合病毒粒子；上皮感染仅在随后发生。因此，宿主的进入是合作的——病毒粒子与上皮细胞结合，允许巨噬细胞感染，这反过来又允许AEC感染。阻断上皮细胞结合的抗体不能阻断宿主的进入：调理作用仅仅提供了另一种进入巨噬细胞的途径。相比之下，抗体阻断膜融合是有效的。因此，合作感染扩展了病毒的趋向性，超出了体外容易感染目标细胞的正常模式；巨噬细胞参与宿主进入需要中和作用于细胞结合的下游。所有的病毒感染都是从宿主进入开始的。在分离培养中广泛研究进入细胞的情况；进入活体寄主的过程更为复杂，也不太为人所知：我们的组织有特定的解剖结构，我们的细胞在大小、形状和行为上与大多数培养细胞有明显不同。呼吸道是病毒感染的常见部位。大小决定了吸入颗粒的位置，病毒大小的颗粒可以到达肺部。横纹肌病毒可以慢性感染人类和经济上重要的动物，并引起肺部疾病。我们使用了一个特征良好的小鼠例子来确定横纹肌病毒如何进入肺部。在高峰期，肺间隙上皮细胞明显感染。然而，它始于巨噬细胞，巨噬细胞通常会清除肺部吸入的碎片。只有上皮细胞表达病毒结合所需的分子，但只有巨噬细胞在结合后内化病毒颗粒；感染涉及这些不同细胞类型之间的相互作用。用抗体阻断上皮感染并不能阻止宿主进入，因为附着的抗体增加了肺巨噬细胞对病毒的摄取；但是一种阻断巨噬细胞感染的抗体是有效的。因此，了解病毒感染如何在正常组织中起作用为其控制提供了重要信息。
Rhadinoviruses establish chronic infections of clinical and economic importance. Several show respiratory transmission and cause lung pathologies. We used Murid Herpesvirus-4 (MuHV-4) to understand how rhadinovirus lung infection might work. A primary epithelial or B cell infection often is assumed. MuHV-4 targeted instead alveolar macrophages, and their depletion reduced markedly host entry. While host entry was efficient, alveolar macrophages lacked heparan - an important rhadinovirus binding target - and were infected poorly ex vivo. In situ analysis revealed that virions bound initially not to macrophages but to heparan+ type 1 alveolar epithelial cells (AECs). Although epithelial cell lines endocytose MuHV-4 readily in vitro, AECs did not. Rather bound virions were acquired by macrophages; epithelial infection occurred only later. Thus, host entry was co-operative - virion binding to epithelial cells licensed macrophage infection, and this in turn licensed AEC infection. An antibody block of epithelial cell binding failed to block host entry: opsonization provided merely another route to macrophages. By contrast an antibody block of membrane fusion was effective. Therefore co-operative infection extended viral tropism beyond the normal paradigm of a target cell infected readily in vitro; and macrophage involvement in host entry required neutralization to act down-stream of cell binding. All viral infections start with host entry. Entry into cells is studied widely in isolated cultures; entry into live hosts is more complicated and less well understood: our tissues have specific anatomical structures and our cells differ markedly from most cultured cells in size, shape and behaviour. The respiratory tract is a common site of virus infection. Size dictates where inhaled particles come to rest, and virus-sized particles can reach the lungs. Rhadinoviruses chronically infect both humans and economically important animals, and cause lung disease. We used a well-characterized murine example to determine how a rhadinovirus enters the lungs. At its peak, infection was prominent in epithelial cells lining the lung air spaces. However it started in macrophages, which normally clear the lungs of inhaled debris. Only epithelial cells expressed the molecules required for virus binding, but only macrophages internalized virus particles after binding; infection involved interaction between these different cell types. Blocking epithelial infection with an antibody did not stop host entry because attached antibodies increase virus uptake by lung macrophages; but an antibody that blocks macrophage infection was effective. Thus, understanding how rhadinovirus infections work in normal tissues provided important information for their control.
登录
查看更多内容
Murid疱疹病毒-4 GH/GL与糖胺聚糖结合。
影响因子：
3.7
作者：
Gillet, Laurent;Colaco, Susanna;Stevenson, Philip G.
通讯作者：
Stevenson, Philip G.
DOI：
10.1084/jem.20062648
发表时间：
2007-07-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Caton ML;Smith-Raska MR;Reizis B
通讯作者：
Reizis B
影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I
影响因子：
6.7
作者：
Frederico, Bruno;Milho, Ricardo;Stevenson, Philip G.
通讯作者：
Stevenson, Philip G.
影响因子：
5.4
作者：
Adler, H;Messerle, M;Koszinowski, UH
通讯作者：
Koszinowski, UH