Brunetti C R, Dingwell K S, Wale C, Graham F L, Johnson D C
McMaster Cancer Research Group, McMaster University, Hamilton, Ontario, Canada.
J Virol. 1998 Apr;72(4):3330-9. doi: 10.1128/JVI.72.4.3330-3339.1998.
Herpes simplex virus (HSV) glycoprotein D (gD) is modified with mannose 6-phosphate (M6P) and binds to M6P receptors (MPRs). MPRs are involved in the well-characterized pathway by which lysosomal enzymes are directed to lysosomes via a network of endosomal membranes. Based on the impaired ability of HSV to form plaques under conditions in which glycoproteins could not interact with MPRs, we proposed that MPRs may function during HSV egress or cell-to-cell spread (C. R. Brunetti, R. L. Burke, B. Hoflack, T. Ludwig, K. S. Dingwell, and D. C. Johnson, J. Virol. 69:3517-3528, 1995). To further analyze M6P modification and intracellular trafficking of gD in the absence of other HSV proteins, adenovirus (Ad) vectors were used to express soluble and membrane-anchored forms of gD. Both membrane-bound and soluble gD were modified with M6P residues and were localized to endosomes that contained the 275-kDa MPR or the transferrin receptor. Similar results were observed in HSV-infected cells. Cell fractionation experiments showed that gD was not present in lysosomes. However, a mutant form of gD and another HSV glycoprotein, gI, that were not modified with M6P were also found in endosomes in HSV-infected cells. Moreover, a substantial fraction of the HSV nucleocapsid protein VP6 was found in endosomes, consistent with accumulation of virions in an endosomal compartment. Therefore, it appears that HSV glycoproteins and virions are directed to endosomes, by M6P-dependent as well as by M6P-independent mechanisms, either as part of the virus egress pathway or by endocytosis from the cell surface.
单纯疱疹病毒（HSV）糖蛋白D（gD）被6-磷酸甘露糖（M6P）修饰，并与M6P受体（MPR）结合。MPR参与了一个已被充分研究的途径，通过该途径，溶酶体酶通过内体膜网络被导向溶酶体。基于在糖蛋白无法与MPR相互作用的条件下HSV形成噬斑的能力受损，我们提出MPR可能在HSV释放或细胞间传播过程中发挥作用（C.R.布鲁内蒂、R.L.伯克、B.霍夫拉克、T.路德维希、K.S.丁韦尔和D.C.约翰逊，《病毒学杂志》69:3517 - 3528，1995年）。为了在没有其他HSV蛋白的情况下进一步分析gD的M6P修饰和细胞内运输，腺病毒（Ad）载体被用于表达可溶性和膜锚定形式的gD。膜结合型和可溶性gD都被M6P残基修饰，并定位于含有275 kDa MPR或转铁蛋白受体的内体。在HSV感染的细胞中也观察到了类似的结果。细胞分级分离实验表明gD不存在于溶酶体中。然而，在HSV感染的细胞的内体中也发现了未被M6P修饰的gD突变形式和另一种HSV糖蛋白gI。此外，在HSV核衣壳蛋白VP6的很大一部分也存在于内体中，这与病毒粒子在内体区室中的积累一致。因此，似乎HSV糖蛋白和病毒粒子通过M6P依赖和M6P非依赖机制被导向内体，这要么是病毒释放途径的一部分，要么是通过从细胞表面的内吞作用。
