Herpesvirus Interactions With Cell Surface Receptors

我们最近证明单纯疱疹病毒（HSV）通过内吞机制成功感染表达糖蛋白D （gD）受体的中国仓鼠卵巢（CHO）细胞和HeLa细胞。我们现在已经定义了这种途径的细胞和病毒需求。完整的、包膜的HSV从细胞表面被摄取到内吞囊泡是快速的（t(1/2) 8到9分钟），并且不依赖于已知的细胞表面gD受体。从表面摄取后，细胞内传染性病毒粒子的恢复稳步增加，直至感染后20分钟（p.i.），这与包膜病毒在细胞内区室的积累相对应。恢复速度在每小时30分钟急剧下降，这表明病毒包膜的丢失是由于衣壳从内吞细胞器渗透到细胞质中。在缺乏gD受体的情况下，内吞病毒粒子不能成功地渗透到细胞质中，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的病毒在转运到细胞核时存在缺陷，传染性降低。因此，与通过直接穿透细胞表面进入细胞类似，HSV通过内吞作用进入细胞是有效的，涉及细胞对病毒颗粒的快速摄取，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.