The viral mechanism of Reye's Syndrome

Younkin, Burrows; Gudzinowicz, B. J.

doi:10.1016/0306-9877(84)90053-7

Cited by 2 publications

(5 citation statements)

References 84 publications

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“…This is consistent with the previous reports of decreased hepatic or nithine carbamoyltransferase activity in RS patients [24][25][26][27]. In conclusion, our results support the hypothesis proposed by Younkin and Gudzinowicz [13] that ODC and the polyamines may be elevated in RS and ele vated levels of polyamines may initiate early Discussion Although polyamines have been reported to be elevated in the plasma of RS patients [11,12], to our knowledge this is the first report describing the levels of polyamines and polyamine-metabolizing enzymes in the liver of RS patients. It is possible that the levels of enzymes determined in our study would have been much higher if the analysis had been carried out immediately.…”

Section: Urea Cycle Enzymessupporting

confidence: 83%

“…Viral infection, either alone or in combi nation with other étiologie agents, may be responsible for the observed increase in he patic ODC activity. A previous report [13] indicates that many viruses activate ODC activity suggesting that, in RS patients, viral infection may contribute to the observed ODC activity. Whether other factors such as drugs or toxins are involved in increased hepatic polyamine biosynthesis in RS pa tients remains to be elucidated.…”

Section: Urea Cycle Enzymesmentioning

confidence: 99%

“…Younkin and Gudzinowicz [13] speculated that vi ruses may activate host cell ornithine decar boxylase (ODC) activity by viral RNA poly merase which in turn would metabolize orni thine into polyamines. Consequently, orni thine would not be available for the urea cycle and therefore carbamoylphosphate will be channeled towards the pyrimidine synthe sis pathway.…”

Section: Introductionmentioning

confidence: 99%

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Hepatic Polyamine Metabolism in Children with Reye’s Syndrome

Mukhopadhyay¹,

Deshmukh²,

Sarnaik³

1991

Enzyme

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Acute mitochondrial insult has been suggested as a primary reason for the clinical, histopathological and biochemical abnormalities seen in Reye’s syndrome. However, the etiology of mitochondrial dysfunction has not been identified. Polyamines have been known to alter the mitochondrial structure and function. Influenza infection may cause an increase in ornithine decarboxylase activity and thereby channel ornithine for polyamine biosynthesis, leading to mitochondrial dysfunction in Reye’s syndrome. To test this hypothesis, the hepatic concentrations of polyamines, polyamine-metabolizing enzymes and urea cycle enzyme activities in Reye’s syndrome patients were determined and compared with patients who died from illnesses other than Reye’s syndrome. The hepatic concentration of putrescine, spermidine and spermine were increased in Reye’s syndrome patients. The activity of ornithine decarboxylase was elevated but, due to the small nubmer of samples, these values did not reach statistical significance. Ornithine carbamoyltransferase activity was decreased in the liver of Reye’s syndrome patients. Our results suggest that increased synthesis of polyamines from ornithine may initiate mitochondrial injury in Reye’s syndrome.

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Section: Urea Cycle Enzymessupporting

confidence: 83%

Section: Urea Cycle Enzymesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hepatic Polyamine Metabolism in Children with Reye’s Syndrome

Mukhopadhyay¹,

Deshmukh²,

Sarnaik³

1991

Enzyme

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“…(18), however, the pathogenesis of this disorder remains incompletely understood in part because the models do not fully mimic the human disease. The association of a prodromal viral illness with Reye's syndrome has prompted speculation regarding a direct interaction of viruses or specific viral gene-products with the host hepatocyte protein synthetic apparatus (8,9). The intracellular mechanisms for such a pathogenetic sequence would not be easily demonstrated using an animal model.…”

Section: The Effect Of Influenza B and Aspirin On Total Protein Synthmentioning

confidence: 99%

“…Total protein synthesis was determined 1,4,8,12, and 24 h after inoculation by incubating the cells in methionine-depleted (1 / 10 standard methionine concentration) MEM with 25 pCi/ ml 35S-methionine (New England Nuclear, Boston, MA) for 30 min at 37" C before harvesting. The cells were washed twice with ice-cold PBS and then collected with a rubber spatula, resuspended in 1 ml PBS, and centrifuged at 1600 rpm for 5 min.…”

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confidence: 99%

Protein Synthesis by HepG2 Cells Infected with Influenza B Virus

et al. 1988

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ABSTRACT. Reye's syndrome is an acute hepatopathy Inasmuch as extrapulmonary dissemination and viremia in and encephalopathy affecting children during the convales-influenza B virus infections are rare (4), it is difficult to postulate cent period of a viral infection, frequently influenza B. The a mechanism by which the hepatic abnormalities in Reye's role of influenza B in the pathogenesis of Reye's syndrome syndrome are induced. In rare instances, virus has been cultured is unknown. To investigate this relationship, an in vitro from the blood or hepatobiliary tissues of children dying from system was designed to examine the interaction of influenza Reye's syndrome, but there are no convincing data to suggest a B virus with a cell line of human hepatocytes (HepG2) direct inflammatory or immunologic component to the hepatic which retains many specific hepatic synthetic characteris-injury (5). tics. HepG2 was capable of supporting a productive infecUsing an animal model of Reye's syndrome described by Davis tion by influenza B, although greater virus inputs were et al. ( 6 ) we recently examined the clinical and histopathologic required than in fully permissive Madin-Darby canine kid-effects of influenza B, given intranasally or intravenously, on ney cells. Because of the recent association of Reye's juvenile BALB/c mice (7). Mice were observed up to 72 h after syndrome with aspirin use, the kinetics of influenza B inoculation. With the exception of hepatic steatosis, no clinical, growth were studied in the presence of acetylsalicylic acid biochemical, or histopathologic features of Reye's syndrome were (25 and 100 fig/ml) and were not found to be altered. demonstrable. The recovery of intact influenza B virus from the Protein synthesis by HepG2 cells was decreased by 80% liver in 25% of mice was unexpected. Inasmuch as other invesin influenza B-infected cells when compared to uninfected tigators have hypothesized a direct interaction of intact virus or controls. Acetylsalicyclic acid, 100 figlml, did not affect a viral gene product with the hepatocyte in Reye's syndrome (8, the rate of 35S-methionine incorporation by infected or 9), the recovery of virus from experimentally infected rats uninfected HepG2 cells. The rates of synthesis of specific prompted the design of an in vitro system for direct assessment proteins (albumin, transferrin, and apoprotein B) by of the interaction of influenza B virus with the hepatocyte. HepG2 cells were determined by immunoprecipitation of 35S-methionine labeled cell lysates. After 12 h of infection, synthesis of all three plasma proteins was decreased by 40-60%. These studies describe a useful system for delin- MATERIALS AND METHODS

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The viral mechanism of Reye's Syndrome

Cited by 2 publications

References 84 publications

Hepatic Polyamine Metabolism in Children with Reye’s Syndrome

Hepatic Polyamine Metabolism in Children with Reye’s Syndrome

Protein Synthesis by HepG2 Cells Infected with Influenza B Virus

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