Loss of the Type I Interferon Pathway Increases Vulnerability of Mice to Genital Herpes Simplex Virus 2 Infection
Loss of the Type I Interferon Pathway Increases Vulnerability of Mice to Genital Herpes Simplex Virus 2 Infection
复制标题
DOI：
10.1128/jvi.01715-10
复制
发表时间：
2011-02-01
影响因子：
5.4
通讯作者：
Carr, Daniel J. J.
中科院分区：
文献类型：
--
作者：
Conrady, Christopher D.;Halford, William P.;Carr, Daniel J. J.
生殖器疱疹的小鼠模型依赖于雌性小鼠的甲羟孕酮治疗，以使阴道腔对单纯疱疹病毒2型（HSV-2）接种敏感。在本研究中，我们报告说，在缺乏甲羟孕酮预处理的情况下，小鼠I型干扰素受体（CD 118（-/-））的A1链缺陷对HSV-2易感。在没有激素预处理的情况下，2,000 PFU的HSV-2临床分离株足以在75% +/- 17%的CD 118（-/-）小鼠的阴道和71% +/- 14%的CD 118（-/-）小鼠的脊髓中建立生产性感染，而相同剂量的HSV-2在感染后第5天的测定中，仅在13% +/-13%的野生型小鼠阴道样本和0%的脊髓样本中复制到可检测水平。CD 118（-/-）小鼠对HSV-2感染的易感性与HSV特异性细胞毒性T淋巴细胞向阴道组织的浸润、γ干扰素（IFN-γ）的局部产生以及T细胞募集趋化因子CCL 5、CXCL 9和CXCL 10的表达显著减少相关。总的来说，这些结果强调了I型干扰素在抵抗生殖器HSV-2感染中的重要作用。
The mouse model of genital herpes relies on medoxyprogesterone treatment of female mice to render the vaginal lumen susceptible to inoculation with herpes simplex virus 2 (HSV-2). In the present study, we report that mice deficient in the A1 chain of the type I interferon receptor (CD118(-/-)) are susceptible to HSV-2 in the absence of medroxyprogesterone preconditioning. In the absence of hormone pretreatment, 2,000 PFU of a clinical isolate of HSV-2 was sufficient to establish a productive infection in the vagina of 75% +/- 17% and in the spinal cord of 71% +/- 14% of CD118(-/-) mice, whereas the same dose of HSV-2 replicated to detectable levels in only 13% +/- 13% of vaginal samples and 0% of spinal cord samples from wild-type mice, as determined at day 5 postinfection. The susceptibility to HSV-2 infection in the CD118(-/-) mice was associated with a significant reduction in the infiltration of HSV-specific cytotoxic T lymphocytes into the vaginal tissue, the local production of gamma interferon (IFN-gamma), and the expression of T cell-recruiting chemokines CCL5, CXCL9, and CXCL10. Collectively, the results underscore the significant contribution of type I IFNs in resistance to genital HSV-2 infection.