Herpes simplex virus 2 ICP0 mutant viruses are avirulent and immunogenic: implications for a genital herpes vaccine.
Herpes simplex virus 2 ICP0 mutant viruses are avirulent and immunogenic: implications for a genital herpes vaccine.
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DOI：
10.1371/journal.pone.0012251
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发表时间：
2010-08-17
期刊：
影响因子：
3.7
通讯作者：
Rakowski B
中科院分区：
文献类型：
--
作者：
Halford WP;Püschel R;Rakowski B
单纯疱疹病毒1型（HSV-1）ICP 0 −突变体对干扰素敏感，无毒力，并可引发针对HSV-1的保护性免疫（Virol J，2006，3：44）。如果单纯疱疹病毒2型（HSV-2）的ICP 0 −突变体表现出类似的特性，这种病毒可能被用于接种生殖器疱疹疫苗。目前的研究就是为了探索这种可能性。构建了几种HSV-2 ICP 0 −突变病毒，并根据三个参数进行了评价：i.干扰素敏感性; ii.小鼠中的毒力;和iii.能够引发针对HSV-2的保护性免疫。特别是一种ICP 0 −突变病毒HSV-2 0ΔNLS，在无毒力和免疫原性之间实现了最佳平衡。HSV-2 0ΔNLS对干扰素敏感。HSV-2 0ΔNLS在接种小鼠眼中复制至低水平，但被先天性Stat 1依赖性宿主免疫应答迅速抑制。HSV-2 0ΔNLS不能从接种部位传播，因此仅产生隐性感染。接种HSV-2 0ΔNLS的小鼠始终产生HSV特异性IgG抗体应答，并始终受到野生型HSV-2致死性攻毒的保护。基于它们的无毒力和免疫原性，我们认为HSV-2 ICP 0 −突变病毒值得考虑，因为它们有可能预防HSV-2和生殖器疱疹的传播。
Herpes simplex virus 1 (HSV-1) ICP0 − mutants are interferon-sensitive, avirulent, and elicit protective immunity against HSV-1 (Virol J, 2006, 3:44). If an ICP0 − mutant of herpes simplex virus 2 (HSV-2) exhibited similar properties, such a virus might be used to vaccinate against genital herpes. The current study was initiated to explore this possibility. Several HSV-2 ICP0 − mutant viruses were constructed and evaluated in terms of three parameters: i. interferon-sensitivity; ii. virulence in mice; and iii. capacity to elicit protective immunity against HSV-2. One ICP0 − mutant virus in particular, HSV-2 0ΔNLS, achieved an optimal balance between avirulence and immunogenicity. HSV-2 0ΔNLS was interferon-sensitive in cultured cells. HSV-2 0ΔNLS replicated to low levels in the eyes of inoculated mice, but was rapidly repressed by an innate, Stat 1-dependent host immune response. HSV-2 0ΔNLS failed to spread from sites of inoculation, and hence produced only inapparent infections. Mice inoculated with HSV-2 0ΔNLS consistently mounted an HSV-specific IgG antibody response, and were consistently protected against lethal challenge with wild-type HSV-2. Based on their avirulence and immunogenicity, we propose that HSV-2 ICP0 − mutant viruses merit consideration for their potential to prevent the spread of HSV-2 and genital herpes.
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影响因子：
3.1
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