Tugizov S, Maidji E, Pereira L
Institute of Virology, D. I. Ivanovsky, Academy of Medical Sciences, Moscow, Russia.
J Gen Virol. 1996 Jan;77 ( Pt 1):61-74. doi: 10.1099/0022-1317-77-1-61.
Human retinal pigment epithelial (RPE) cells, which are permissive for human cytomegalovirus (HCMV) replication, were used to evaluate virus infection from apical and basolateral membranes of polarized cells. Tests of HCMV infectivity showed that the apical membrane was 20-30-fold more susceptible to infection than the basolateral membrane; in contrast, both membranes were equally susceptible to infection by herpes simplex virus type 1 (HSV-1). Neutralizing monoclonal antibodies (MAbs) to HCMV glycoprotein B (gB) blocked penetration of virions into polarized RPE cells. This indicated that gB has a function in fusion of the virion envelope with the apical membrane of these cells, as it has with the cell membrane of unpolarized human fibroblasts. In contrast to HSV-1-infected RPE cells, the paracellular permeability of polarized RPE cells changed slowly following infection with HCMV. Confocal microscopy examination of HCMV-infected RPE cells revealed that the pattern of ZO-1 staining was altered at late times. Addition of gB-specific neutralizing MAbs to the apical and basolateral membranes of HCMV-infected RPE cells failed to inhibit plaque development; this indicated that progeny virions infect adjacent cells before disassembly of tight junctions and are sequestered from neutralization during spread across lateral cell membranes. The finding that progeny HCMV virions cross lateral cell membranes, which differ substantially in protein composition from apical membranes, suggests that polarized RPE cells contain multiple receptors for HCMV.
人视网膜色素上皮（RPE）细胞允许人巨细胞病毒（HCMV）复制，被用于评估极化细胞顶膜和基底外侧膜的病毒感染情况。HCMV感染性测试表明，顶膜比基底外侧膜对感染的敏感性高20 - 30倍；相比之下，两种膜对1型单纯疱疹病毒（HSV - 1）感染的敏感性相同。针对HCMV糖蛋白B（gB）的中和单克隆抗体（MAb）可阻断病毒粒子进入极化的RPE细胞。这表明gB在病毒粒子包膜与这些细胞顶膜的融合中发挥作用，就像它在未极化的人成纤维细胞膜中发挥的作用一样。与HSV - 1感染的RPE细胞不同，极化的RPE细胞在感染HCMV后，其细胞旁通透性变化缓慢。对HCMV感染的RPE细胞进行共聚焦显微镜检查发现，ZO - 1染色模式在后期发生了改变。向HCMV感染的RPE细胞的顶膜和基底外侧膜添加gB特异性中和MAb未能抑制噬斑形成；这表明子代病毒粒子在紧密连接解体之前感染相邻细胞，并在跨细胞膜侧向传播过程中免受中和作用。子代HCMV病毒粒子穿过蛋白质组成与顶膜有很大差异的侧向细胞膜，这一发现表明极化的RPE细胞含有多种HCMV受体。
