Navarro D, Paz P, Pereira L
Division of Oral Biology, School of Dentistry, University of California San Francisco 94143-0512.
Virology. 1992 Jan;186(1):99-112. doi: 10.1016/0042-6822(92)90064-v.
Herpes simplex virus 1 glycoprotein B (gB) is one of 10 glycoproteins in the virion envelope and in the membranes of infected cells. It is required for infection of cells in culture and functions in penetration of the cell by fusing the virion envelope with the plasma membrane. In studies to map the functional domains on HSV-1 gB, we reported that epitopes of potent neutralizing antibodies cluster in three major antigenic domains, D1, D2, and D5a. D1 contains continuous epitopes in the very amino terminus of gB. D2 comprises discontinuous epitopes that are assembled on gB derivatives 457 amino acids in length. D5a contains discontinuous epitopes that map between amino acids 600 and 690. We have now analyzed the function of these domains in virion infectivity by a detailed examination of the effects of 16 neutralizing antibodies on virion adsorption, penetration, plaque development, and cell fusion. Our results are as follows. (i) Ten antibodies with complement-independent neutralizing activity blocked penetration of virions into cells but not their adsorption to the cell surface. Treating cell-bound, neutralized virus with the fusogenic agent polyethylene glycol promoted their entry into cells. (ii) Ten antibodies with complement-dependent and -independent neutralizing activity interfered with plaque development by preventing spread of virus from infected to neighboring uninfected cells. (iii) Nine neutralizing antibodies, all complement-independent, prevented cell fusion induced by strain HFEM syn. We conclude that domains mapping in three regions of gB function in penetration of virions into cells, and that most neutralizing antibodies to these domains also block cell-to-cell spread of virus and cell fusion. The findings that three complement-independent neutralizing antibodies that blocked penetration did not inhibit plaque development, and that only one of these blocked cell fusion, indicate that the cell-to-cell spread of virus and cell fusion are related processes, but not identical to the penetration function.
单纯疱疹病毒1型糖蛋白B（gB）是病毒体包膜以及受感染细胞膜中10种糖蛋白之一。它是细胞培养感染所必需的，通过使病毒体包膜与质膜融合来发挥细胞穿透功能。在绘制HSV-1 gB功能域的研究中，我们报告称，强效中和抗体的表位聚集在三个主要抗原域D1、D2和D5a中。D1在gB的极氨基末端包含连续表位。D2包含不连续表位，这些表位组装在长度为457个氨基酸的gB衍生物上。D5a包含位于氨基酸600至690之间的不连续表位。我们现在通过详细检查16种中和抗体对病毒体吸附、穿透、蚀斑形成和细胞融合的影响，分析了这些域在病毒体感染性中的功能。我们的结果如下。（i）10种具有非补体依赖性中和活性的抗体可阻断病毒体进入细胞，但不影响其吸附到细胞表面。用融合剂聚乙二醇处理结合在细胞上的中和病毒可促进其进入细胞。（ii）10种具有补体依赖性和非补体依赖性中和活性的抗体通过阻止病毒从感染细胞传播到邻近未感染细胞来干扰蚀斑形成。（iii）9种中和抗体均为非补体依赖性，可阻止HFEM syn株诱导的细胞融合。我们得出结论，位于gB三个区域的功能域在病毒体进入细胞的过程中发挥作用，并且针对这些域的大多数中和抗体也会阻断病毒的细胞间传播和细胞融合。三种阻断穿透的非补体依赖性中和抗体不抑制蚀斑形成，且其中只有一种阻断细胞融合，这一发现表明病毒的细胞间传播和细胞融合是相关过程，但与穿透功能不同。
