Herpesvirus Interactions With Cell Surface Receptors

我们最近证明，单纯疱疹病毒（HSV）成功地感染中国仓鼠卵巢（CHO）细胞表达糖蛋白D（gD）受体和HeLa细胞的内吞机制。我们现在已经确定了该途径的细胞和病毒要求。完整的，包膜HSV从细胞表面进入内吞囊泡的摄取是快速的（t（1/2）为8至9分钟），并独立于已知的细胞表面gD受体。从表面摄取后，细胞内感染性病毒体的恢复稳定增加至感染后20分钟（p.i.），这对应于包膜病毒在细胞内区室中的积累。在注射后30分钟恢复率急剧下降，这表明病毒包膜的丧失是衣壳从内吞细胞器穿透进入胞质溶胶的结果。在没有gD受体的情况下，内吞的病毒粒子没有成功地渗透到胞质溶胶中，而是被转运到溶酶体中进行降解。缺乏病毒糖蛋白gB、gD或gH-gL的病毒在向细胞核的运输中有缺陷，并且具有降低的感染性。因此，类似于通过直接穿透细胞表面进入，HSV通过内吞作用进入细胞是有效的，涉及病毒颗粒的快速细胞摄取，并且需要gB、gD和gH-gL。

We recently demonstrated that herpes simplex virus (HSV) successfully infects Chinese hamster ovary (CHO) cells expressing glycoprotein D (gD) receptors and HeLa cells by an endocytic mechanism. We have now defined cellular and viral requirements of this pathway. Uptake of intact, enveloped HSV from the cell surface into endocytic vesicles was rapid (t(1/2) of 8 to 9 min) and independent of the known cell surface gD receptors. Following uptake from the surface, recovery of intracellular, infectious virions increased steadily up to 20 min postinfection (p.i.), which corresponds to accumulation of enveloped virus in intracellular compartments. There was a sharp decline in recovery by 30 min p.i., suggesting loss of the virus envelope as a result of capsid penetration from endocytic organelles into the cytosol. In the absence of gD receptors, endocytosed virions did not successfully penetrate into the cytosol but were instead transported to lysosomes for degradation. Viruses that lack viral glycoproteins gB, gD, or gH-gL were defective in transport to the nucleus and had reduced infectivity. Thus, similar to entry via direct penetration at the cell surface, HSV entry into cells by endocytosis is efficient, involves rapid cellular uptake of viral particles, and requires gB, gD, and gH-gL.