Construction, phenotypic analysis, and immunogenicity of a UL5/UL29 double deletion mutant of herpes simplex virus 2
Construction, phenotypic analysis, and immunogenicity of a UL5/UL29 double deletion mutant of herpes simplex virus 2
复制标题
DOI：
10.1128/jvi.74.17.7963-7971.2000
复制
发表时间：
2000-09-01
影响因子：
5.4
通讯作者：
Knipe, DM
中科院分区：
文献类型：
--
作者：
Da Costa, X;Kramer, MF;Knipe, DM
大量研究表明，单纯疱疹病毒(HSV)复制缺陷突变株可诱导动物系统对野生型HSV攻击产生保护性免疫。然而，所有这些研究都使用了具有单一突变的病毒。由于多个稳定的突变为活疫苗提供了最佳的安全水平，我们认为需要将更多的突变改造成HSV-2和生殖器疱疹的候选疫苗株。因此，我们分离了一株在两个病毒DNA复制蛋白基因UL5和UL29上存在缺失突变的HSV-2毒株。由此产生的双缺失突变病毒株dl5-29在正常的猴子或人类细胞中无法形成斑块或产生任何可检测到的单周期产量。然而，DL5-29表达的基因产物与野生型病毒或单一突变病毒几乎相同，在小鼠体内诱导的抗体效价与单一缺失突变病毒诱导的抗体效价相当。因此，分离出一个基本基因有两个突变的HSV突变株是可行的，并且安全性提高，但仍具有高度的免疫原性。
A number of studies have shown that replication-defective mutant strains of herpes simplex virus (HSV) can induce protective immunity in animal systems against wild-type HSV challenge. However, all of those studies used viruses with single mutations. Because multiple, stable mutations provide optimal levels of safety for live vaccines, we felt that additional mutations needed to be engineered into a candidate vaccine strain for HSV-2 and genital herpes. We therefore isolated an HSV-2 strain with deletion mutations in two viral DNA replication protein genes, UL5 and UL29. The resulting double deletion mutant virus strain, dl5-29, fails to form plaques or to give any detectable single cycle yields in normal monkey or human cells. Nevertheless, dl5-29 expresses nearly the same pattern of gene products as the wild-type virus or the single mutant viruses and induces antibody titers in mice that are equivalent to those induced by single deletion mutant viruses. Therefore, it is feasible to isolate a mutant HSV strain with two mutations in essential genes and with an increased level of safety but which is still highly immunogenic.