|Levander, Orville - BHNRC COLLABORATOR, BELTS|
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 7, 2008
Publication Date: May 8, 2008
Citation: Smith, A.D., Botero, S., Levander, O. 2008. Copper deficiency increases the virulence of amyocarditic and myocarditic strains of cocksackievirus B3 in mice. Journal of Nutrition. 138(5):849-55. Interpretive Summary: Deficiency in several nutrients, including copper and selenium, is associated with increased levels of oxidative stress and also can decrease immune function. It has been shown that a deficiency in selenium or vitamin E can make a common illness caused by a virus, coxsackievirus B3, more severe. We were interested to see if a similar effect would be seen with a copper deficiency that also increases oxidative stress. Mice were made deficient in copper and infected with the virus. At three and seven days after infection the virus was found at higher levels in the heart of copper deficient mice compared to copper adequate mice. The copper deficient mice also had more damage to the heart muscle. Evaluation of immune function in copper deficient mice indicated less specific antibody being produced against the virus. Since it is known that the antibody response is important for elimination of the virus, it appears that copper deficiency interfers with the normal production of these antibodies and leads to higher viral infection with a more severe disease outcome. This information is important to nutritionists that recommend balanced diets for optimal health, and scientists that study the effect of nutrition on immune function and control of infectious agents.
Technical Abstract: Deficiency in several trace elements, including copper and selenium, is associated with increased levels of oxidative stress. Copper deficiency also has been shown to impair immune function. Previous work by others demonstrated that passage of an amyocarditic or myocarditic strain of coxsackievirus B3 (CVB3) through selenium or vitamin E deficient mice led to increased cardiac pathology. To determine if a copper deficiency would similarly alter the pathogenesis of CVB3 infections, copper adequate or deficient mice were infected with an amyocarditic or myocarditic strain of CVB3. Heart viral titers were elevated at days 3 and 7 post-infection in copper deficient mice infected with the myocarditic CVB3 strain (CVB3/20), but only at day 7 in deficient mice infected with the amyocarditic CVB3 strain (CVB3/0) compared to copper adequate controls. Copper deficient mice infected with either strain of CVB3 had increased cardiac pathology compared to copper adequate controls. In contrast to the genomice sequence changes observed in CVB3/0 obtained from hearts of selenium or vitamin E deficient mice, sequences of viruses isolated from copper adequate and deficient mice were identical. Heart cytokine expression was elevated in copper deficient CVB3-infected mice compared to infected controls. Circulating CVB3-specific IgG2a but not IgM levels were decreased in copper deficient mice. Thus, copper deficiency is associated with an increased inflammatory response but decreased acquired immune response to CVB3 infection that results in increased cardiac pathology.