Inagaki-Ohara K, Iwasaki T, Watanabe D, Kurata T, Nishiyama Y
Laboratory of Virology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, 466-8550, Nagoya, Japan.
Vaccine. 2001 Oct 12;20(1-2):98-104. doi: 10.1016/s0264-410x(01)00311-5.
We investigated the effects of US2 and US3 deficiencies of herpes simplex virus type 2 (HSV-2) on host immunity in a murine model of genital herpes infection. Viral clearance from the vaginal mucosa was more rapid in mice infected with a US3-deficient mutant L1BR1 as compared with a wild-type 186 or YY2 (US2-deficient mutant) infection, although there was no significant difference among them in initial growth in the early stage of infection. Flow cytometric studies revealed that the number of vaginal mononuclear cells in L1BR1-infected mice was significantly greater than that in 186- or YY2-infected mice. Dendritic cells, macrophages and T cells were induced more rapidly and in greater numbers within the vaginas of L1BR1-infected mice. Moreover, the levels of IL-12 and IFN-gamma increased in L1BR1-infected mice over levels in 186-infected mice. These results indicate that a US3 deficiency alters the induction of the host immune response; therefore, the inactivation of US3 may be a promising strategy in the development of novel vaccines for genital herpes.
我们在单纯疱疹病毒2型（HSV-2）生殖器疱疹感染的小鼠模型中，研究了HSV-2的US2和US3缺陷对宿主免疫的影响。与野生型186或YY2（US2缺陷突变体）感染相比，感染US3缺陷突变体L1BR1的小鼠阴道黏膜中的病毒清除更快，尽管在感染早期它们的初始生长没有显著差异。流式细胞术研究表明，L1BR1感染小鼠的阴道单核细胞数量显著多于186或YY2感染的小鼠。在L1BR1感染小鼠的阴道内，树突状细胞、巨噬细胞和T细胞的诱导更快且数量更多。此外，L1BR1感染小鼠中IL-12和IFN-γ的水平高于186感染小鼠。这些结果表明，US3缺陷改变了宿主免疫反应的诱导；因此，US3的失活可能是开发新型生殖器疱疹疫苗的一种有前景的策略。
