Majde J A, Brown R K, Jones M W, Dieffenbach C W, Maitra N, Krueger J M, Cady A B, Smitka C W, Maassab H F
Office of Naval Research, Arlington, VA 22217.
Microb Pathog. 1991 Feb;10(2):105-15. doi: 10.1016/0882-4010(91)90071-h.
While many of the molecular events in viral replication are well studied, the molecular mechanisms by which viral infections trigger such constitutional symptoms as fever and 'malaise' are unknown. The hypothesis that these viral constitutional symptoms can be triggered by the toxic action of dsRNA associated with viral replication was investigated. Total lung RNA from mice acutely infected with PR8 influenza virus, but not from sham-infected mice, was shown to induce fever and altered sleep (excess slow-wave sleep, enhanced amplitudes of electroencephalographic slow waves, and reduced rapid eye movement sleep) when injected into the rabbit brain. Viral-associated dsRNA was shown to be responsible for the rabbit responses by differential nuclease digestion. Influenza viral dsRNA was directly demonstrated in the active lung RNA preparations by reverse transcriptase-polymerase chain reaction techniques. The time course of the responses paralleled those seen in the same model inoculated with nanogram quantities of the synthetic dsRNA polyriboinosinic-polyribocytidylic acid and suggested that they were mediated by induced cytokines. A model for the role of viral-associated dsRNA in eliciting both local cytotoxicity and viral constitutional symptoms is presented.
虽然病毒复制过程中的许多分子事件已得到充分研究，但病毒感染引发发热和“不适”等全身症状的分子机制尚不清楚。本研究探讨了一种假说，即这些病毒全身症状可能由与病毒复制相关的双链RNA（dsRNA）的毒性作用所触发。将急性感染PR8流感病毒的小鼠的肺总RNA（而非假感染小鼠的肺总RNA）注射到兔脑内后，可引发发热并改变睡眠（慢波睡眠增多、脑电图慢波振幅增强、快速眼动睡眠减少）。通过核酸酶消化差异实验表明，病毒相关的dsRNA是兔出现这些反应的原因。利用逆转录-聚合酶链反应技术在活性肺RNA制剂中直接检测到了流感病毒dsRNA。这些反应的时间进程与接种纳克量合成dsRNA聚肌苷酸-聚胞苷酸的同一模型中观察到的情况相似，提示它们是由诱导的细胞因子介导的。本文提出了一个关于病毒相关dsRNA在引发局部细胞毒性和病毒全身症状中作用的模型。
