Carr D J, Veress L A, Noisakran S, Campbell I L
Department of Microbiology, Immunology, and Parasitology, Louisiana State University Medical Center, New Orleans 70112-1393, USA.
J Immunol. 1998 Nov 1;161(9):4859-65.
Type I IFNs (i.e., IFN-alpha and IFN-beta) play a key role in the host's innate defense against viral pathogens. To examine the biologic relevance of IFN-alpha to a viral pathogen within the confines of the nervous system, IFN-alpha1 transgenic mice whose transgene is under the control of the glial fibrillary acidic protein promoter (GFAP-IFN-alpha, astrocyte specific) were examined for resistance to an ocular herpes simplex virus type 1 (HSV-1) infection. GFAP-IFN-alpha mice expressed significantly higher levels of IFN-alphabeta (533 U) in the trigeminal ganglion compared with nontransgenic mice (70 U) 72 h postinfection that corresponded with a significant reduction in the mRNA expression of the HSV-1 immediate early gene infected cell polypeptide 27 and late gene VP16, as well as the chemokines monocyte-chemoattractant protein-1 and cytokine response gene-2 in the eye and trigeminal ganglion. Six days postinfection, the viral load and the expression of infected cell polypeptide 27, CD8, RANTES, IFN-gamma, and IFN-alpha mRNA levels were reduced in the trigeminal ganglion of GFAP-IFN-alpha mice compared with the wild-type mice. Following the establishment of HSV-1 latency (i.e., 30 days postinfection), only one of nine (11%) GFAP-IFN-alpha mice was found to be latent compared with seven of eight (88%) of the wild-type mice, as determined by the expression of the latency-associated transcript RNAs. Likewise, only three of nine GFAP-IFN-alpha mice screened showed seroconversion by day 30 postinfection compared with nine of ten wild-type mice screened. Collectively, the results show that the IFN-alpha1 transgenic mice are less susceptible to acute HSV-1 infection and the establishment of viral latency.
I型干扰素（即α干扰素和β干扰素）在宿主对病毒病原体的固有防御中起关键作用。为了在神经系统范围内研究α干扰素与病毒病原体的生物学相关性，对转基因受胶质纤维酸性蛋白启动子（GFAP-α干扰素，星形胶质细胞特异性）控制的α干扰素1转基因小鼠进行了抗眼部单纯疱疹病毒1型（HSV-1）感染的检测。感染后72小时，GFAP-α干扰素小鼠三叉神经节中αβ干扰素的表达水平（533 U）显著高于非转基因小鼠（70 U），这与HSV-1立即早期基因感染细胞多肽27和晚期基因VP16以及眼部和三叉神经节中趋化因子单核细胞趋化蛋白-1和细胞因子反应基因-2的mRNA表达显著降低相对应。感染后6天，与野生型小鼠相比，GFAP-α干扰素小鼠三叉神经节中的病毒载量以及感染细胞多肽27、CD8、调节激活正常T细胞表达和分泌的趋化因子、γ干扰素和α干扰素mRNA水平均降低。在HSV-1潜伏期建立后（即感染后30天），通过潜伏期相关转录RNA的表达测定，发现9只GFAP-α干扰素小鼠中只有1只（11%）处于潜伏状态，而8只野生型小鼠中有7只（88%）处于潜伏状态。同样，在感染后30天筛选的9只GFAP-α干扰素小鼠中只有3只出现血清转化，而在筛选的10只野生型小鼠中有9只出现血清转化。总体而言，结果表明α干扰素1转基因小鼠对急性HSV-1感染和病毒潜伏期的建立较不敏感。
