Levine B, Griffin D E
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Virol. 1992 Nov;66(11):6429-35. doi: 10.1128/JVI.66.11.6429-6435.1992.
Little is known about the relationship between recovery from acute viral encephalitis and the clearance of viral genetic material from the central nervous system. In a mouse model of Sindbis virus encephalitis, we have previously shown that clearance of infectious virus is mediated by antibody-induced restriction of viral gene expression rather than by cytotoxic destruction of virally infected cells. To explore whether Sindbis virus genomes persist in mouse brain after the clearance of infectious virus, we used reverse transcriptase-polymerase chain reaction amplification methods to detect Sindbis virus RNA in brain samples from immunocompetent BALB/c and antibody-treated immunodeficient scid/CB17 mice. RNA sequences from both the nonstructural region (NSP1 gene) and structural regions (E2 gene) of Sindbis virus were detected in the brains of all BALB/c and antibody-treated scid mice examined at 1, 2, and 3 months after infection. Additional BALB/c mouse brains were also positive at 8, 12, and 17 months after infection. To determine whether persistent RNA was capable of resuming unrestricted replication in the absence of the continuous presence of antiviral antibodies, viral titers were measured in the brains of scid mice at 1, 2, 3, and 6 months after antibody treatment. Viral reactivation was seen in scid mice treated with hyperimmune serum or a low dose of monoclonal antibody to the E2 envelope glycoprotein, but not in mice treated with a high dose of monoclonal antibody to E2. Replication of infectious virus isolated from scid mouse brain could be restricted by repeat treatment with immune serum, indicating that viral reactivation is not due to antibody-escape mutations. These results demonstrate that Sindbis virus can persist long term in a nonproductive form in mouse brain and suggest that the humoral immune response plays an important role in preventing viral reactivation.
关于急性病毒性脑炎的恢复与病毒遗传物质从中枢神经系统清除之间的关系，目前所知甚少。在辛德毕斯病毒脑炎的小鼠模型中，我们先前已表明，感染性病毒的清除是由抗体诱导的病毒基因表达受限介导的，而非通过对病毒感染细胞的细胞毒性破坏。为了探究在感染性病毒清除后，辛德毕斯病毒基因组是否会在小鼠脑中持续存在，我们使用逆转录 - 聚合酶链反应扩增方法，检测了免疫功能正常的BALB/c小鼠以及经抗体处理的免疫缺陷scid/CB17小鼠脑样本中的辛德毕斯病毒RNA。在感染后1、2和3个月检查的所有BALB/c小鼠以及经抗体处理的scid小鼠的脑中，均检测到了辛德毕斯病毒非结构区（NSP1基因）和结构区（E2基因）的RNA序列。另外，感染后8、12和17个月的BALB/c小鼠脑也呈阳性。为了确定在没有抗病毒抗体持续存在的情况下，持续存在的RNA是否能够恢复不受限制的复制，我们在抗体处理后1、2、3和6个月测量了scid小鼠脑中的病毒滴度。在用高免疫血清或低剂量的抗E2包膜糖蛋白单克隆抗体处理的scid小鼠中观察到了病毒再激活，但在用高剂量的抗E2单克隆抗体处理的小鼠中未观察到。从scid小鼠脑中分离出的感染性病毒的复制可通过用免疫血清重复处理而受到限制，这表明病毒再激活并非由于抗体逃逸突变。这些结果表明，辛德毕斯病毒可以在小鼠脑中以非增殖形式长期持续存在，并表明体液免疫反应在预防病毒再激活中起重要作用。
