Herpes Simplex Virus Type 1 Glycoprotein E Domains Involved in Virus Spread and Disease
Herpes Simplex Virus Type 1 Glycoprotein E Domains Involved in Virus Spread and Disease
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DOI：
10.1128/jvi.74.15.6712-6719.2000
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发表时间：
2000-08
影响因子：
5.4
通讯作者：
Charles E. Saldanha;J. Lubinski;Claudia Martin;T. Nagashunmugam;Liyang Wang;H. van der Keyl;R. Tal-Singer;Harvey M Friedman
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文献类型：
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作者：
Charles E. Saldanha;J. Lubinski;Claudia Martin;T. Nagashunmugam;Liyang Wang;H. van der Keyl;R. Tal-Singer;Harvey M Friedman
摘要 单纯疱疹病毒 1 型 (HSV-1) 糖蛋白 E (gE) 作为免疫球蛋白 G (IgG) Fc 结合蛋白发挥作用，参与病毒传播。此前，我们研究了一种 gE 突变病毒，该病毒的 IgG Fc 结合能力受损，但传播能力完好，而另一种病毒的两种活性均正常。为了进一步评估 gE 在传播中的作用，通过在 gE 位置 210 的 IgG Fc 结合结构域外部或在位置 380 的 IgG Fc 结合结构域内引入接头插入突变，构建了另外两种突变病毒。两种突变病毒在体外表皮细胞中的传播均受到损害；然而，380突变病毒的受损程度明显更高，并且与gE无效病毒一样有缺陷。将 gE 突变病毒接种到小鼠胁腹中，以测量接种部位的表皮疾病、病毒传播至背根神经节以及病毒从神经节传播回皮肤以产生带状疱疹样病变。两种突变病毒的接种部位和带状疱疹样部位的疾病均减少，但 380 突变病毒的情况更严重。此外，病毒培养和实时定量PCR证明，380突变病毒到达神经节的能力严重受损。结果表明，氨基酸 380 周围的结构域对于传播和 IgG Fc 结合都很重要，并表明该结构域是抗病毒治疗或疫苗的潜在靶点。
ABSTRACT Herpes simplex virus type 1 (HSV-1) glycoprotein E (gE) functions as an immunoglobulin G (IgG) Fc binding protein and is involved in virus spread. Previously we studied a gE mutant virus that was impaired for IgG Fc binding but intact for spread and another that was normal for both activities. To further evaluate the role of gE in spread, two additional mutant viruses were constructed by introducing linker insertion mutations either outside the IgG Fc binding domain at gE position 210 or within the IgG Fc binding domain at position 380. Both mutant viruses were impaired for spread in epidermal cells in vitro; however, the 380 mutant virus was significantly more impaired and was as defective as gE null virus. gE mutant viruses were inoculated into the murine flank to measure epidermal disease at the inoculation site, travel of virus to dorsal root ganglia, and spread of virus from ganglia back to skin to produce zosteriform lesions. Disease at the inoculation and zosteriform sites was reduced for both mutant viruses, but more so for the 380 mutant virus. Moreover, the 380 mutant virus was highly impaired in its ability to reach the ganglia, as demonstrated by virus culture and real-time quantitative PCR. The results indicate that the domain surrounding amino acid 380 is important for both spread and IgG Fc binding and suggest that this domain is a potential target for antiviral therapy or vaccines.