Interferon type I receptor-deficient mice have altered disease symptoms in response to influenza virus.
The role of type I interferons (IFNs) in mediation of acute viral symptoms (fever, somnolence, anorexia, etc.) is unknown. To determine the role of type I IFN in selected symptom development, body temperature and sleep responses to a marginally lethal dose of X-31 influenza virus were examined in mice with a targeted mutation of the IFN receptor type I (IFN-RI knockouts) and compared to wild-type 129 SvEv control mice. Mice were monitored for 48 h to determine baseline temperature and sleep profiles prior to infection, and then for 9 days following infection. Hypothermic responses to virus were perceptible beginning at 64 h post-infection (PI) and were more marked in KO mice until 108 h, when hypothermia became more exaggerated in wild-type controls. Temperatures of wild-type mice continued to decline through day 9 while temperatures in IFN-RI KO mice stabilized. Time spent in non-rapid eye movement sleep (NREMS) increased in KO mice when hypothermia was marked and then returned to baseline levels, while NREMS continued to increase in wild-type mice through day 9. Other sleep parameters [time spent in rapid eye movement sleep (REMS), relative NREMS EEG slow wave activity, NREMS EEG power density] were all reduced in wild-type mice compared to KOs from days 3 to 8 while REMS low frequency EEG power density increased in wild-type relative to KOs. In conclusion, our results indicate that the presence of functional type I IFN slightly ameliorates disease symptoms early in the X-31 infection while exacerbating disease symptoms later in the infection.
Traynor
Tim R
TR
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, P.O. Box 646520, Pullman, WA 99164-6520, USA.
Majde
Jeannine A
JA
Bohnet
Stewart G
SG
Krueger
James M
JM
D000704:Analysis of Variance; D000818:Animals; D001833:Body Temperature Regulation / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D017471:Receptors, Interferon / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012894:Sleep Stages / Q000276:immunology*
D007370:Interferon Type I; D017471:Receptors, Interferon