Nöske K, Bilzer T, Planz O, Stitz L
Institut für Virologie, Justus-Liebig-Universität Giessen, Tübingen, Germany.
J Virol. 1998 May;72(5):4387-95. doi: 10.1128/JVI.72.5.4387-4395.1998.
Persistent Borna disease virus infection of the brain can be prevented by treatment of naive rats with a virus-specific CD4+ T-cell line prior to infection. In rats receiving this treatment, only a transient low-level encephalitis was seen compared to an increasingly inflammatory reaction in untreated infected control rats. Virus replication was found in the brain for several days after infection before the virus was cleared from the central nervous system. The loss of infectivity from the brain was confirmed by negative results by reverse transcription-PCR with primers for mRNA, by in situ hybridization for both genomic and mRNA, and by immunohistology. Most importantly, in vitro assays revealed that the T-cell line used for transfusion had no cytotoxic capacity. The kinetics of virus clearance were paralleled by the appearance of CD8+ T cells and the expression of perforin in the brain. Testing of lymphocytes isolated from the brains of CD4+ T-cell-treated rats after challenge revealed high cytotoxic activity due to the presence of CD8+ cytotoxic T cells at time points when brain lymphocytes from infected control rats induced low-level cytolysis of target cells. Neutralizing antiviral antibodies and gamma interferon were shown not to be involved in the elimination of virus from the brain.
在未感染的大鼠感染前，用病毒特异性CD4 + T细胞系进行治疗可预防脑内持续性博尔纳病病毒感染。与未治疗的感染对照大鼠中日益增强的炎症反应相比，接受这种治疗的大鼠仅出现短暂的低水平脑炎。感染后数天内在脑中发现病毒复制，之后病毒才从中枢神经系统清除。通过使用mRNA引物的逆转录 - PCR阴性结果、基因组和mRNA的原位杂交以及免疫组织学，证实了脑内传染性的丧失。最重要的是，体外试验表明用于输血的T细胞系没有细胞毒性能力。病毒清除的动力学与CD8 + T细胞的出现以及脑中穿孔素的表达平行。对攻击后从接受CD4 + T细胞治疗的大鼠脑中分离的淋巴细胞进行检测发现，在感染对照大鼠的脑淋巴细胞诱导靶细胞低水平细胞溶解的时间点，由于存在CD8 + 细胞毒性T细胞，具有高细胞毒性活性。已表明中和抗病毒抗体和γ干扰素不参与从脑中清除病毒。
