Resistance of interleukin-1beta-deficient mice to fatal Sindbis virus encephalitis.
Interleukin-1beta (IL-1beta) concentrations are frequently elevated in central nervous system (CNS) viral infections, but the pathophysiologic significance of such elevations is not known. To examine the role of IL-1beta in CNS viral pathogenesis, we compared the natural histories of IL-1beta-deficient and wild-type 129 SV(ev) mice infected with a neurovirulent viral strain, neuroadapted Sindbis virus (NSV). We found that the incidence of severe paralysis and death was markedly decreased in NSV-infected IL-1beta-/- mice compared to NSV-infected wild-type mice (4 versus 88%, P < 0.001). Despite this marked difference in clinical outcome, no differences in numbers of apoptotic cells or presence of histopathologic lesions in the brains of moribund wild-type mice and those of clinically healthy IL-1beta-/- mice could be detected. These results suggest that IL-1beta deficiency is protective against fatal Sindbis virus infection by a mechanism that does not involve resistance to CNS virus-induced apoptosis or histopathology.
Liang
X H
XH
Department of Medicine, Columbia University College of Physicians & Surgeons, New York, New York 10032, USA.
Goldman
J E
JE
Jiang
H H
HH
Levine
B
B
D018354:Alphavirus Infections / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000473:pathology; D018792:Encephalitis, Viral / Q000473:pathology*; D007375:Interleukin-1 / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D012845:Sindbis Virus