Accumulation of mini-plasmin in the cerebral capillaries causes vascular invasion of the murine brain by a pneumotropic influenza A virus: implications for influenza-associated encephalopathy
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D. Yao
Abstract
The infectivity and pathogenicity of influenza virus are primarily determined by host cellular trypsin-type processing proteases which cleave the viral membrane fusion glycoprotein hemagglutinin (HA). Therefore the distribution of the processing protease is a major determinant of the infectious organ tropism. The common epidemic human influenza A virus is pneumotropic and the HA processing proteases tryptase Clara, mini-plasmin, tryptase TC30 and ectopic anionic trypsin have all been isolated from mammalian airways. However, the pneumotropic influenza virus occasionally causes severe brain edema, particularly in children presenting with Reyes syndrome treated with aspirin, or in children with influenza associated encephalopathy without antipyretic treatment. We have observed that, after influenza virus infection, the accumulation of mini-plasmin in the cerebral capillaries in mice with a congenital or acquired abnormality of mitochondrial β-oxidation mimicking the pathological findings of Reyes syndrome, causes an invasion and multiplication of the pneumotropic influenza virus at these same locations. From these findings, we hypothesize that the accumulated mini-plasmin modifies the brain capillaries from a non-permissive to a permissive state, thereby allowing multiplication of pneumotropic influenza virus. In addition, mini-plasmin proteolytically destroys the bloodbrain barrier. These pathologic findings, consistent with encephalopathy in mice with a systemic impairment of β-oxidation, may have implications for human influenza encephalopathy.
Copyright © 2004 by Walter de Gruyter GmbH & Co. KG
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