Tishon A, Southern P J, Oldstone M B
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
J Immunol. 1988 Feb 15;140(4):1280-4.
Viruses that cause in vivo persistent infections need to selectively compromise the host's immunologic surveillance machinery in order to survive. To understand the molecular basis of how this is accomplished we have analyzed persistent virus infection by lymphocytic choriomeningitis in its normal host, the mouse. Earlier we noted by infectious center analysis that five in 10(4) lymphocytes carried by persistently infected mice contained infectious materials throughout the course of infection. A previous publication extended these results, in BALB mice by showing that the L3T4+ lymphocyte subset in lymph nodes and spleens was predominantly involved. Using cDNA labeled probes to the viral genome and in situ hybridization we report that 1 to 2% of circulating lymphocytes from several mouse strains contain viral RNA sequences for the three viral structural genes. By FACS analysis, the Thy-1.2+, L3T4+ subset primarily harbors virus while viral sequences are usually not detected in the Lyt-2+ subset as early as 6 days after initiating infection in newborns and throughout the course of the persistence. These findings suggest that incomplete, presumably defective, virus is generated in a subset of Th lymphocytes during persistent infection and that during this time infection of cytotoxic T cell subsets is minimal.
能引起体内持续性感染的病毒为了存活，需要选择性地破坏宿主的免疫监视机制。为了了解这一过程的分子基础，我们通过分析淋巴细胞性脉络丛脑膜炎病毒在其正常宿主小鼠体内的持续性感染来进行研究。之前我们通过感染中心分析发现，持续性感染小鼠体内每10⁴个淋巴细胞中就有5个在整个感染过程中都含有感染性物质。之前的一篇论文在BALB小鼠中扩展了这些结果，表明淋巴结和脾脏中的L3T4⁺淋巴细胞亚群主要受到影响。我们使用针对病毒基因组的cDNA标记探针和原位杂交技术报告称，来自几种小鼠品系的循环淋巴细胞中有1%至2%含有三种病毒结构基因的病毒RNA序列。通过荧光激活细胞分选分析，Thy-1.2⁺、L3T4⁺亚群主要携带病毒，而早在新生小鼠感染后6天及整个持续感染过程中，在Lyt-2⁺亚群中通常检测不到病毒序列。这些发现表明，在持续性感染期间，Th淋巴细胞亚群中产生了不完整的、可能有缺陷的病毒，并且在此期间细胞毒性T细胞亚群的感染极少。
