GLYCOPROTEIN-E AND GLYCOPROTEIN-I FACILITATE NEURON-TO-NEURON SPREAD OF HERPES-SIMPLEX VIRUS
GLYCOPROTEIN-E AND GLYCOPROTEIN-I FACILITATE NEURON-TO-NEURON SPREAD OF HERPES-SIMPLEX VIRUS
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DOI：
10.1128/jvi.69.11.7087-7098.1995
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发表时间：
1995-11-01
影响因子：
5.4
通讯作者：
JOHNSON, DC
中科院分区：
文献类型：
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作者：
DINGWELL, KS;DOERING, LC;JOHNSON, DC
两种单纯疱疹病毒 (HSV) 糖蛋白 E 和 I（gE 和 gI）形成异寡聚体，充当 Fc 受体，并促进病毒在上皮组织中以及某些培养细胞之间的细胞间传播。相比之下，细胞外病毒感染细胞不需要gE-gI。 HSV 糖蛋白 go 酸 gJ 由邻近基因编码，go 是病毒进入细胞和细胞间传播所必需的，而 gJ 尚未被证明会影响这些过程。由于 HSV 感染神经元并且显然在突触连接处传播，因此确定 go、gE、gI 和 gJ 是否对于病毒的神经元间转移也很重要是很有意义的。我们通过将无法表达这些糖蛋白的突变病毒注射到大鼠眼的玻璃体中，测试了这些糖蛋白在 1 型 HSV (HSV-1) 神经元到神经元传播中的作用。在视网膜富含神经元的层和大脑的主要视网膜接收区域中测量了病毒感染的传播情况。野生型HSV-1和gJ(-)突变体在突触连接的视网膜神经元之间快速传播，并有效感染大脑的主要视网膜受体区域。 go突变体源自互补细胞，仅感染少数神经元，并且不会在视网膜或大脑中扩散。无法表达gE或gI的突变体在视网膜内传播的能力明显受到限制，在视网膜中产生的病毒数量减少了10倍，并且无法有效地传播到大脑。此外，与野生型HSV-1相比，gE(-)和gI(-)突变体在大鼠三叉神经节来源的神经元培养物中的细胞间传播效率低下。总之，我们的结果表明，gE-gI 异寡聚体是通过突触连接的神经元途径进行有效的神经元间传递所必需的。
Two herpes simplex virus (HSV) glycoproteins E and I (gE and gI) form a heterooligomer which acts as an Fc receptor and also facilitates cell-to-cell spread of virus in epithelial tissues and between certain cultured cells. By contrast, gE-gI is not required for infection of cells by extracellular virus. HSV glycoproteins go acid gJ are encoded by neighboring genes, and go is required for both virus entry into cells and cell-to-cell spread, whereas gJ has not been shown to influence these processes. Since HSV infects neurons and apparently spreads across synaptic junctions, it was of interest to determine whether go, gE, gI, and gJ are also important for interneuronal transfer of virus. We tested the roles of these glycoproteins in neuron-to-neuron transmission of HSV type 1 (HSV-1) by injecting mutant viruses unable to express these glycoproteins into the vitreous body of the rat eye. The spread of virus infection was measured in neuron-rich layers of the retina and in the major retinorecipient areas of the brain. Wild-type HSV-1 and a gJ(-) mutant spread rapidly between synaptically linked retinal neurons and efficiently infected major retinorecipient areas of the brain. go mutants, derived from complementing cells, infected only a few neurons and did not spread in the retina or brain. Mutants unable to express gE or gI were markedly restricted in their ability to spread within the retina, produced 10-fold-less virus in the retina, and spread inefficiently to the brain. Furthermore, when compared with wild-type HSV-1, gE(-) and gI(-) mutants spread inefficiently from cell to cell in cultures of neurons derived from rat trigeminal ganglia. Together, our results suggest that the gE-gI heterooligomer is required for efficient neuron-to-neuron transmission through synaptically linked neuronal pathways.