Glycoprotein gp110 of Epstein-Barr virus determines viral tropism and efficiency of infection
Glycoprotein gp110 of Epstein-Barr virus determines viral tropism and efficiency of infection
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DOI：
10.1073/pnas.232381299
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发表时间：
2002-11-12
影响因子：
11.1
通讯作者：
Delecluse, HJ
中科院分区：
文献类型：
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作者：
Neuhierl, B;Feederle, R;Delecluse, HJ
Epstein-Barr病毒（EBV）基因组已在淋巴瘤和上皮或间质起源的肿瘤（如鼻咽癌或平滑肌肉瘤）中检测到。因此，毫无疑问，EBV在体内可以感染许多谱系的细胞，而其体外感染谱似乎主要局限于B淋巴细胞。我们在这里表明EBV BALF4基因产物，糖蛋白gp110，显著增强EBV感染人类细胞的能力。Gp110（高）病毒在感染淋巴细胞或上皮细胞方面的效率是Gp110（高）病毒的100倍。此外，gp110（high）病毒感染癌细胞系HeLa和T细胞淋巴瘤细胞系Molt-4，这两种细胞先前被认为对EBV感染是难治的。对几种病毒分离株的分析表明，在这些菌株中，成熟病毒粒子中存在的BALF4的量显着不同。在一些菌株中，gp110不仅在细胞核上表达，而且在细胞膜上表达。在病毒裂解期，gp110的异源表达既不改变病毒浓度，也不影响病毒与细胞的结合。似乎gp110在病毒粘附到其细胞靶标后起着至关重要的作用。gp110是决定EBV对非b细胞感染的重要毒力因子。因此，使用gp110（high）病毒将有助于确定eb病毒在B淋巴细胞以外的靶细胞范围，并提供一个有用的体外模型来评估eb病毒在这些细胞中的致癌潜力。
The Epstein-Barr virus (EBV) genome has been detected in lymphomas and in tumors of epithelial or mesenchymal origin such as nasopharyngeal carcinoma or leiomyosarcoma. Thus, there is little doubt that EBV can infect cells of numerous lineages in vivo, in contrast to its in vitro infectious spectrum, which appears restricted predominantly to B lymphocytes. We show here that the EBV BALF4 gene product, the glycoprotein gp110, dramatically enhances the ability of EBV to infect human cells. gp110(high) viruses were up to 100 times more efficient than their gp110(high) counter-parts in infecting lymphoid or epithelial cells. In addition, gp110(high) viruses infected the carcinoma cell line HeLa and the T cell lymphoma cell line Molt-4, both previously thought to be refractory to EBV infection. Analysis of several virus isolates showed that the amount of BALF4 present within mature virions markedly differed among these strains. In some strains, gp110 was found expressed during lytic replication not only at the nuclear but also at the cellular membrane. Heterologous expression of gp110 during the virus lytic phase neither altered virus concentration nor affected virus binding to cells. It appears that gp110 plays a crucial role after the virus has adhered to its cellular target. gp110 constitutes an important virulence factor that determines infection of non-B cells by EBV. Therefore, the use of gp110(high) viruses will help to determine the range of the target cells of EBV beyond B lymphocytes and provide a useful in vitro model to assess the oncogenic potential of EBV in these cells.