Impaired long-chain fatty acid metabolism in mitochondria causes brain vascular invasion by a non-neurotropic epidemic influenza A virus in the newborn/suckling period: implications for influenza-associated encephalopathy
| Autor: | Mayumi Shiota, Hiroshi Yamada, Hiroshi Kido, Yuushi Okumura, Ye Chen, Masamichi Kuwajima, Dengfu Yao |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Clinical Biochemistry
Encephalopathy Vascular permeability Mitochondrion Biology medicine.disease_cause Virus Mice chemistry.chemical_compound Virus antigen medicine Influenza A virus Animals Carnitine Molecular Biology DNA Primers Brain Diseases Base Sequence Fatty acid metabolism Reverse Transcriptase Polymerase Chain Reaction Influenza A Virus H3N2 Subtype Fatty Acids Brain Cell Biology General Medicine medicine.disease Immunohistochemistry Animals Suckling Mitochondria Mice Inbred C57BL Animals Newborn chemistry Blood-Brain Barrier Immunology medicine.drug |
| Zdroj: | Molecular and Cellular Biochemistry. 299:85-92 |
| ISSN: | 1573-4919 0300-8177 |
| Popis: | The neuropathogenesis of influenza-associated encephalopathy in children and Reye's syndrome remains unclear. A surveillance effort conducted during 2000-2003 in South-West Japan reveals that almost all fatal and handicapped influenza-associated encephalopathy patients exhibit a disorder of mitochondrial beta-oxidation with elevated serum acylcarnitine ratios (C(16:0)+C(18:1))/C(2). Here we show invasion by a non-neurotropic epidemic influenza A H3N2 virus in cerebral capillaries with progressive brain edema after intranasal infection of mice having impaired mitochondrial beta-oxidation congenitally or posteriorly in the newborn/ suckling periods. Mice genetically lacking of carnitine transporter OCTN2, resulting in carnitine deficiency and impaired beta-oxidation, exhibited significant higher virus-genome numbers in the brain, accumulation of virus antigen exclusively in the cerebral capillaries and increased brain vascular permeability compared to in wild type mice. Mini-plasmin, which proteolytically potentiates influenza virus multiplication in vivo and destroys the blood-brain barrier, accumulated with virus antigen in the brain capillaries of OCTN2-deficient mice but only a little in wild-type mice. These results suggest that the impaired mitochondrial beta-oxidation changes the susceptibility to a non-neurotropic influenza A virus as to multiplication in the brain capillaries and to cause brain edema. These pathological findings in the brain of mice having impaired mitochondrial beta-oxidation after influenza virus infection may have implications for human influenza-associated encephalopathy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink