GLYCOPROTEIN-B OF HUMAN CYTOMEGALOVIRUS PROMOTES VIRION PENETRATION INTO CELLS, TRANSMISSION OF INFECTION FROM CELL-TO-CELL, AND FUSION OF INFECTED-CELLS

GLYCOPROTEIN-B OF HUMAN CYTOMEGALOVIRUS PROMOTES VIRION PENETRATION INTO CELLS, TRANSMISSION OF INFECTION FROM CELL-TO-CELL, AND FUSION OF INFECTED-CELLS
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DOI:
10.1006/viro.1993.1575
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发表时间:
1993-11-01
期刊:
影响因子:
3.7
通讯作者:
PEREIRA, L
PEREIRA, L
中科院分区:
医学3区
文献类型:
--
作者:
NAVARRO, D;PAZ, P;PEREIRA, L

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人巨细胞病毒(HCMV)糖蛋白B(gB)是病毒粒子包膜中丰富的糖蛋白,在人感染和免疫动物中激发中和抗体。使用一组具有中和活性的gB单克隆抗体,我们详细分析了这些抗体阻断HCMV感染的机制。研究了12种具有补体非依赖性中和活性的抗体对病毒粒子附着于细胞表面、病毒粒子渗透到细胞中、感染从细胞到细胞的传播以及感染细胞的融合的影响。所有的补体非依赖性抗体阻断病毒粒子渗透到细胞中,但对病毒粒子附着到细胞表面没有影响。最有效的中和抗体也限制了感染从细胞到细胞的传播。HCMV感染的U373胶质母细胞瘤细胞的融合被阻断的所有,但两个中和抗体的gB,这表明感染细胞的融合是类似的,但不相同的病毒粒子包膜与细胞膜的融合,发生在病毒粒子进入。我们的研究结果提供了第一个证据表明,HCMV gB是一种多功能糖蛋白,促进病毒粒子渗透到细胞中,从细胞到细胞的感染传播,并感染U373细胞的融合。
Human cytomegalovirus (HCMV) glycoprotein B (gB) is an abundant glycoprotein in the virion envelope that elicits neutralizing antibodies in human infection and in immunized animals. Using a panel of monoclonal antibodies to gB with neutralizing activity, we analyzed in detail the mechanisms by which these antibodies block HCMV infection. Twelve antibodies with complement-independent neutralizing activity were studied for their effect on the attachment of virions to the cell surface, virion penetration into cells, the transmission of infection from cell to cell, and fusion of infected cells. All of the complement-independent antibodies blocked penetration of virions into cells but had no effect on virion attachment to the cell surface. The most potent neutralizing antibodies also limited the spread of infection from cell to cell. Fusion of HCMV-infected U373 glioblastoma cells was blocked by all but two of the neutralizing antibodies to gB, suggesting that fusion of infected cells is similar but not identical to the fusion of the virion envelope with the cell membrane that occurs during virion entry. Our findings provide the first evidence that HCMV gB is a multifunctional glycoprotein that promotes virion penetration into cells, the transmission of infection from cell to cell, and fusion of infected U373 cells.