|Nelva, Bryant - FDA|
|Hines, Fred - FDA|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: April 23, 2003
Publication Date: March 1, 2004
Citation: Nelva, B., Levander, O.A., Hines, F., Smith, A.D. 2004. Study of the effect of copper deficiency on cvb3/0 and cvb3/20 infections: The light microscopic evaluation of the pancreata and hearts of c3h/hej mice [abstract]. Toxicologic Pathology. 32(1):146. Technical Abstract: In a previous study in mice fed a diet deficient in selenium developed myocarditis when infected with a normally benign (amyocarditic) strain of Coxsackievirus serotype B3 (CVB3/0). Copper (Cu) is a critical component of many essential enzymes and antioxidant functions. In the present experiment, we examined the effects of a copper deficient diet on the virulence of CV23/0 (amyocarditic strain of CVB3) and CVB3/20 (myocarditic strain of CVB3). Mice were given free access-to a casein-based copper adequate diet or copper deficient diet. Deficiency was confirmed by a reduction in ceruloplasmin levels by 95% in the mice fed the deficient diet. After 30 days on the diet, the mice were injected with I.OE5 TCID50 of CVB3/0 or CVB3/20 or sham infected. At days 5 and 10 post-inoculation, the mice were euthanized and various tissues were harvested for virus titer analysis and light microscopic evaluation. Light microscopic evaluation revealed lesions primarily in the pancreata and hearts. These changes consisted of pancreatic necrosis and depletion characterized by multifocal to diffuse loss of exocrine acinar cells through an apoptotic mechanism, and multifocal to locally extensive myocardial fibrosis and mineralization. The degree of severity of these lesions was more apparent in the CVB3/20 infected mice, and the amount of fibrosis was diminished in Cu deficient mice. These results indicate that copper status selectively influences the degree of virus-induced heart damage and may selectively influence the degree of pancreatic damage through a postulated oxidative stress mechanism.