Synthetic influenza viral double-stranded RNA induces an acute-phase response in rabbits

Numerous studies have characterized the physiological effects of synthetic, high-molecular-weight, homopolymeric, double-stranded RNA (dsRNA), particu larly polyriboinosinic.polyribocytidylic acid [Carter and De Clercq (1974): Science 186:1172-1178], but limited information exists regarding the physi ological effects of dsRNA of viral composition and size. In this report, we determined sleep and fever responses of rabbits to intracerebroventricular injection of different doses of synthetic viral dsRNA (either 108 base pai rs or 661 base pairs) derived from the N-terminal sequence of gene segment 3 of the A/PR/8/34-H1N1 (PR8) influenza virus. Both the108-mer and the 661- mer dsRNAs increased nonrapid eye movement sleep, suppressed rapid eye move ment sleep, and induced fever. The 661-mer dsRNA had more potent somnogenic and pyrogenic effects than the 108-mer dsRNA on the basis of weight. Neith er single-stranded RNA from the corresponding sequences had significant eff ects on sleep or brain temperature. These results demonstrate for the first time that low-molecular-weight, viral dsRNA has the stability in vivo that is required to induce the fever and sleep changes found in natural viral i nfections, and the hypothesis is supported that virus-associated dsRNA may be responsible for initiating the acute-phase response during viral infecti ons. (C) 1999 Wiley-Liss, Inc.