Infection of BALB/c mice with a herpes simplex virus type 1 recombinant virus expressing IFN-γ driven by the LAT promoter
Infection of BALB/c mice with a herpes simplex virus type 1 recombinant virus expressing IFN-γ driven by the LAT promoter
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DOI：
10.1006/viro.2002.1609
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发表时间：
2002-10-10
期刊：
影响因子：
3.7
通讯作者：
Wechsler, SL
中科院分区：
文献类型：
--
作者：
Ghiasi, H;Osorio, Y;Wechsler, SL
构建了表达鼠干扰素-γ（IFN-γ）的重组单纯疱疹病毒1型（HSV-IFN-γ），以研究IFN-γ表达对HSV-1感染小鼠的影响。通过将鼠IFN-γ的基因插入潜伏相关转录物（LAT）启动子控制下的LAT阴性重组病毒中来产生HSV-IFN-γ。ELISA分析证实重组病毒在组织培养中表达高水平的IFN-γ。与野生型和LAT（-）亲本株相比，重组HSV-IFN-γ具有降低的毒力，这通过在BALB/c小鼠中眼部和ip感染后的死亡来判断。HSV-IFN-γ的复制在组织培养和小鼠眼中是野生型的。此外，小鼠三叉神经节（TG）和脑中的HSV-IFN-γ滴度峰值对于所有病毒都是相似的，尽管HSV-IFN-γ在眼部感染小鼠的TG和脑中出现的时间早于任一亲本病毒。在用UV灭活病毒刺激后，来自HSV-IFN-γ感染小鼠的淋巴细胞似乎在整个感染的第一周产生稳定水平的白细胞介素-2（IL-2）和IFN-γ，而来自野生型和LAT阴性亲本病毒dLAT 2903的淋巴细胞中的IL-2和IFN-γ水平随时间变化。同样与来自野生型和dLAT 2903感染小鼠的淋巴细胞相反，来自HSV-IFN-γ感染小鼠的淋巴细胞不产生可检测的IL-4。在用重组IFN-γ（rIFN-γ）刺激后，与来自对照病毒感染的小鼠的淋巴细胞相比，来自HSV-IFN-γ感染的小鼠的淋巴细胞产生更高水平的IFN-γ。最后，HSV-IFN-γ诱导的CTL和细胞增殖与两种亲本病毒相似。因此，本报告证明：（i）HSV-IFN-γ具有降低的神经毒力，尽管在感染小鼠的TG中具有增强的复制;（ii）HSV-IFN-γ没有增强CTL活性，高于在野生型感染小鼠中所见的;和（iii）HSV-IFN-γ诱导T（H）1型细胞因子应答。(C)2002 Elsevier Science（美国）。
A recombinant herpes simplex virus type 1 expressing murine interferon-gamma (IFN-gamma) was constructed (HSV-IFN-gamma) to study the effect of IFN-gamma expression on HSV-1 infection of mice. HSV-IFN-gamma was created by inserting the gene for murine IFN-gamma under the control of the latency-associated transcript (LAT) promoter in a LAT-negative recombinant virus. ELISA analysis confirmed that the recombinant virus expressed high levels of IFN-gamma in tissue culture. The recombinant HSV-IFN-gamma had reduced virulence compared with the wild-type and LAT(-) parental strains as judged by death following ocular and ip infections in BALB/c mice. Replication of HSV-IFN-gamma was wild type in tissue culture and mouse eyes. In addition, peak HSV-IFN-gamma titers in mouse trigeminal ganglia (TG) and brain were similar for all viruses, although HSV-IFN-gamma appeared in the TG and brains of ocularly infected mice earlier than either parental virus. Following stimulation with UV-inactivated virus, lymphocytes from HSV-IFN-gamma-infected mice appeared to produce a steady level of interleukin-2 (IL-2) and IFN-gamma throughout the first week of infection, while the IL-2 and IFN-gamma levels in lymphocytes from wild-type and the LAT-negative parental virus, dLAT2903, varied over time. Also in contrast to lymphocytes from wild-type and dLAT2903-infected mice, lymphocytes from HSV-IFN-gamma-infected mice produced no detectable IL-4. Following stimulation with recombinant IFN-gamma (rIFN-gamma), lymphocytes from HSV-IFN-gamma-infected mice produced higher levels of IFN-gamma, as compared to lymphocytes from control virus-infected mice. Finally, CTL and cell proliferation induced by HSV-IFN-gamma were similar to those of both parental viruses. Thus, this report demonstrates that (i) HSV-IFN-gamma had reduced neurovirulence, despite having enhanced replication in the TG of infected mice; (ii) HSV-IFN-gamma did not enhance CTL activity above that seen in wild-type infected mice; and (iii) HSV-IFN-gamma induced a T(H)1 pattern of cytokine response. (C) 2002 Elsevier Science (USA).