Oxidant stress responses in influenza virus pneumonia: gene expression and transcription factor activation. Choi, Augustine M. K., Katharine Knobil, Sherrie L. Otterbein, Deborah A. Eastman, and David B. Jacoby. Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, Johns Hopkins University, Baltimore, Maryland 21224
APStracts 3:0082L, 1996.
The pathogenesis of influenza virus infections of the lungs is in part mediated by oxidative stress. Such infections might therefore be expected to induce expression of stress-response genes and genes encoding antioxidant enzymes and to activate transcriptional regulatory proteins. Mice (C57Bl/6 and C3H/HeJ) were infected intranasally with influenza virus A/PR/8/34 (H1N1). Expression of the genes encoding the antioxidant enzymes manganese superoxide dismutase, indoleamine-2,3-dioxygenase, heme oxygenase-1, and glutathione peroxidase were increased in the lungs of virus-infected animals. Copper/zinc superoxide dismutase and catalase mRNA were not induced by viral infection. Activation of the transcriptional regulatory proteins AP-1, C/EBP, and NF-kB (which are known to be affected by oxidant stress), was demonstrated by electrophoretic mobility shift assay after viral infection. In the case of manganese superoxide dismutase, despite increased gene expression enzyme activity was not increased. In constrast, for heme oxygenase-1 both mRNA and activity were increased. C3H/HeJ and C57Bl/6 mice, which are known to have different responses to other types of oxidant stress, also differed in their responses to viral infection. Induction of heme oxygenase-1 expression was greater in C57Bl/6 mice than in C3H/HeJ mice, although inhibiting this enzyme did not alter virus -induced mortality. In contrast, indoleamine 2,3-dioxygenase was more strongly induced in C3H/HeJ mice. Activation of NF-kB was much more marked in C57Bl/6 mice than in C3H/HeJ mice. Although virus replication and inflammatory responses were equivalent in the two strains, lung injury (as measured by wet to dry weight ratios) and mortality were greater in C3H/HeJ mice than in C57Bl/6 mice, a difference that may be related to differing oxidant stress responses. Thus influenza pneumonia causes an oxidant stress response in the lungs, the nature of which is determined in part by the genetic background of the host. 

Received 18 July 1995; accepted in final form 9 April 1996.
APS Manuscript Number L225-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 June 96