Mueller Scott N, Jones Claerwen M, Chen Weisan, Kawaoka Yoshihiro, Castrucci Maria R, Heath William R, Carbone Francis R
Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia.
J Virol. 2003 Feb;77(4):2445-51. doi: 10.1128/jvi.77.4.2445-2451.2003.
The immune response to cutaneous herpes simplex virus type 1 (HSV-1) infection begins with remarkable rapidity. Activation of specific cytotoxic T lymphocytes (CTL) begins within hours of infection, even though the response within the draining lymph nodes peaks nearly 5 days later. HSV gene products are classified into three main groups, alpha, beta, and gamma, based on their kinetics and requirements for expression. In C57BL/6 mice, the immunodominant epitope from HSV is derived from glycoprotein B (gB(498-505)). While gB is considered a gamma or "late" gene product, previous reports have indicated that some level of gene expression may occur soon after infection. Using brefeldin A as a specific inhibitor of viral antigen presentation to major histocompatibility complex class I-restricted CTL, we have formally addressed the timing of gB peptide expression in an immunologically relevant manner following infection. Presentation of gB peptide detected by T-cell activation was first observed within 2 h of infection. Comparison with another viral epitope expressed early during infection, HSV-1 ribonucleotide reductase, demonstrated that gB is presented with the same kinetics as this classical early-gene product. Moreover, this rapidity of gB expression was further illustrated via rapid priming of naïve transgenic CD8(+) T cells in vivo after HSV-1 infection of mice. These results establish that gB is expressed rapidly following HSV-1 infection, at levels capable of effectively stimulating CD8(+) T cells.
对皮肤单纯疱疹病毒1型(HSV-1)感染的免疫反应开始得非常迅速。特异性细胞毒性T淋巴细胞(CTL)的激活在感染后数小时内就开始了,尽管引流淋巴结内的反应在近5天后达到峰值。HSV基因产物根据其表达动力学和要求分为三个主要组,即α、β和γ组。在C57BL/6小鼠中,来自HSV的免疫显性表位源自糖蛋白B(gB(498-505))。虽然gB被认为是一种γ或“晚期”基因产物,但先前的报告表明,感染后不久可能会出现一定水平的基因表达。使用布雷菲德菌素A作为病毒抗原呈递给主要组织相容性复合体I类限制性CTL的特异性抑制剂,我们以免疫学相关的方式正式研究了感染后gB肽表达的时间。通过T细胞激活检测到的gB肽呈递在感染后2小时内首次观察到。与感染早期表达的另一种病毒表位HSV-1核糖核苷酸还原酶进行比较,表明gB的呈递动力学与这种经典的早期基因产物相同。此外,通过对HSV-1感染小鼠后的幼稚转基因CD8(+) T细胞进行快速体内启动,进一步说明了gB表达的快速性。这些结果表明,HSV-1感染后gB迅速表达,其水平能够有效刺激CD8(+) T细胞。