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.

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 Reye's 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 beta-oxidation mimicking the pathological findings of Reye's 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 blood-brain barrier. These pathologic findings, consistent with encephalopathy in mice with a systemic impairment of beta-oxidation, may have implications for human influenza encephalopathy.

journal_name

Biol Chem

journal_title

Biological chemistry

authors

Yao D,Chen Y,Kuwajima M,Shiota M,Kido H

doi

10.1515/BC.2004.057

keywords:

subject

Has Abstract

pub_date

2004-06-01 00:00:00

pages

487-92

issue

6

eissn

1431-6730

issn

1437-4315

journal_volume

385

pub_type

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