[Deleterious pathogenic mechanism involving host response in influenza virus infection in mice].
In the influenza virus infected mice there is a host response which involves free radical generation particularly in the host lung. First, superoxide generation was elevated excessive extent, 200-600 fold in the alveolar lavage fluid (BALF), by induction of xanthine oxidase which becomes maximal at about 8 days after infection while virus yield becomes maximum on day 4. Mice start to die on day 9 although the virus in BALF is undetectable; thus virus disease in the absence of virus. Second, inducible form of nitric oxide synthetase is also triggered exactly in parallel to xanthine oxidase. This indicates NO and O2- is produced simultaneously implicating the formation of peroxynitrite (ONOO-) due to a rapid reaction between NO + O2-. Consequently nitration of lung tissue by ONOO- was demonstrated. ONOO- is also found much toxic than O2- or H2O2 in the cultured cells. Third, proteases are involved in various ways in this infection; activation of xanthine dehydrogenose to xanthine oxidase, activation of viral infectivity and triggering of bradykinin generation and inflammation by activating prekallikrein. Lastly, activation of matrix procollagenase (proMMP) by ONOO- and NO2, generated above, was suggested, which will damage connective tissue. Thus all events involving proteases will augment viral pathogenesis.
Maeda
H
H
Department of Microbiology, Kumamoto University School of Medicine.
D000818:Animals; D010450:Endopeptidases / Q000378:metabolism; D004789:Enzyme Activation; D005609:Free Radicals / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D005609:Free Radicals; D013481:Superoxides; D009569:Nitric Oxide; D010450:Endopeptidases