Herpes simplex virus gE/gI sorts nascent virions to epithelial cell junctions, promoting virus spread
Herpes simplex virus gE/gI sorts nascent virions to epithelial cell junctions, promoting virus spread
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DOI：
10.1128/jvi.75.2.821-833.2001
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发表时间：
2001-01-01
影响因子：
5.4
通讯作者：
Brunetti, C
中科院分区：
文献类型：
--
作者：
Johnson, DC;Webb, M;Brunetti, C
α疱疹病毒通过皮肤组织和在突触连接的神经元回路内迅速传播。病毒颗粒在上皮组织中的传播涉及穿过细胞连接的运动。单纯疱疹病毒（HSV）、水痘-带状疱疹病毒（VZV）和伪狂犬病病毒（PRV）都利用两种糖蛋白gE和gI的复合物在细胞间移动。HSV gE/gI似乎主要（如果不是唯一的话）在极化细胞如上皮细胞和神经元中起作用，而不在非极化细胞或形成较不广泛的细胞连接的细胞中起作用。在这里，我们表明，HSV颗粒被专门分选到细胞连接和少数病毒粒子到达极化上皮细胞的顶端表面。gE/gI参与此排序。缺乏gE或仅gE的胞质结构域的突变型HSV病毒体在细胞连接处被发现;相反，它们被发现在顶端表面和细胞培养液中并在细胞质中积累。AP-1网格蛋白衔接子复合物的一种组分mu 1B参与将蛋白质分选至基底外侧表面，其参与将PRV颗粒靶向至侧表面。这些结果与最近的观察结果有关，即（i）HSV gE/gI在感染的早期特异性定位于trans-Golgi网络（TGN），但在中期至晚期移动到细胞连接处（T. McMillan和D. C.约翰逊，J.病毒学，（ii）PRV gE/gI参与核衣壳进入细胞质膜囊泡的过程（A. R Brack，B. G. Klupp，H.格兰佐夫河蒂拉巴西湖W. Enquist和T. C. R Mettenleiter，J. Virol. 74：4004-4016，2000）。因此，gE/gI的胞质结构域与AP-1细胞分选机制之间的相互作用导致糖蛋白积聚并聚集到被分选到细胞侧面的特定TGN隔室中。将病毒颗粒递送到细胞连接处将有望增强病毒传播并使病毒能够避开宿主的免疫防御。
Alphaherpesviruses spread rapidly through dermal tissues and within synaptically connected neuronal circuitry. Spread of virus particles in epithelial tissues involves movement across cell junctions. Herpes simplex virus (HSV), varicella-zoster virus (VZV), and pseudorabies virus (PRV) all utilize a complex of two glycoproteins, gE and gI, to move from cell to cell. HSV gE/gI appears to function primarily, if not exclusively, in polarized cells such as epithelial cells and neurons and not in nonpolarized cells or cells that form less extensive cell junctions. Here, we show that HSV particles are specifically sorted to cell junctions and few virions reach the apical surfaces of polarized epithelial cells. gE/gI participates in this sorting. Mutant HSV virions lacking gE or just the cytoplasmic domain of gE were rarefy found at cell junctions; instead, they were found on apical surfaces and in cell culture fluids and accumulated in the cytoplasm. A component of the AP-1 clathrin adapter complexes, mu 1B, that is involved in sorting of proteins to basolateral surfaces was involved in targeting of PRV particles to lateral surfaces. These results are related to recent observations that (i) HSV gE/gI localizes specifically to the trans-Golgi network (TGN) during early phases of infection but moves out to cell junctions at intermediate to late times (T. McMillan and D. C. Johnson, J. Virol., in press) and (ii) PRV gE/gI participates in envelopment of nucleocapsids into cytoplasmic membrane vesicles (A. R Brack, B. G. Klupp, H. Granzow, R. Tirabassi, L. W. Enquist, and T. C. R Mettenleiter, J. Virol. 74:4004-4016, 2000). Therefore, interactions between the cytoplasmic domains of gE/gI and the AP-1 cellular sorting machinery cause glycoprotein accumulation and envelopment into specific TGN compartments that are sorted to lateral cell surfaces. Delivery of virus particles to cell junctions would be expected to enhance virus spread and enable viruses to avoid host immune defenses.