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单纯疱疹病毒 2 ICP0 突变病毒是无毒性和免疫原性的：对生殖器疱疹疫苗的影响。

Herpes simplex virus 2 ICP0 mutant viruses are avirulent and immunogenic: implications for a genital herpes vaccine.

机构信息

Department of Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, Illinois, United States of America.

出版信息

PLoS One. 2010 Aug 17;5(8):e12251. doi: 10.1371/journal.pone.0012251.

DOI:10.1371/journal.pone.0012251
PMID:20808928
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2923193/
Abstract

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 0DeltaNLS, achieved an optimal balance between avirulence and immunogenicity. HSV-2 0DeltaNLS was interferon-sensitive in cultured cells. HSV-2 0DeltaNLS 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 0DeltaNLS failed to spread from sites of inoculation, and hence produced only inapparent infections. Mice inoculated with HSV-2 0DeltaNLS 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.

摘要

单纯疱疹病毒 1（HSV-1）ICP0（-）突变体对干扰素敏感，无毒性，并能引发针对 HSV-1 的保护性免疫（Virol J，2006，3：44）。如果单纯疱疹病毒 2（HSV-2）的 ICP0（-）突变体表现出类似的特性，那么这种病毒可能被用于预防生殖器疱疹。本研究旨在探讨这种可能性。构建了几种 HSV-2 ICP0（-）突变病毒，并从三个方面对其进行了评估：i.干扰素敏感性；ii.在小鼠中的毒力；iii. 对 HSV-2 产生保护性免疫的能力。特别是一种 ICP0（-）突变病毒，HSV-2 0DeltaNLS，在毒力和免疫原性之间达到了最佳平衡。HSV-2 0DeltaNLS 在培养细胞中对干扰素敏感。HSV-2 0DeltaNLS 在接种小鼠的眼部复制到低水平，但被先天的、Stat 1 依赖性的宿主免疫反应迅速抑制。HSV-2 0DeltaNLS 不能从接种部位传播，因此只产生不明显的感染。接种 HSV-2 0DeltaNLS 的小鼠持续产生 HSV 特异性 IgG 抗体反应，并持续免受野生型 HSV-2 的致死性攻击的保护。基于其毒力和免疫原性，我们提出 HSV-2 ICP0（-）突变体病毒值得考虑用于预防 HSV-2 和生殖器疱疹的传播。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/652c/2923193/e29ce76df6d8/pone.0012251.g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/652c/2923193/562c38cbff32/pone.0012251.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/652c/2923193/7e2db4b88562/pone.0012251.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/652c/2923193/e29ce76df6d8/pone.0012251.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/652c/2923193/cb121326d3d3/pone.0012251.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/652c/2923193/e322681dcc51/pone.0012251.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/652c/2923193/edf94dbe6652/pone.0012251.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/652c/2923193/dd0677ae174f/pone.0012251.g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/652c/2923193/562c38cbff32/pone.0012251.g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/652c/2923193/e29ce76df6d8/pone.0012251.g008.jpg

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