Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 12/1/2006
Publication Date: 3/6/2006
Citation: Smith, A.D., Botero, S., Levander, O.A. 2006. Copper deficiency increases the virulence of coxsackievirus B3 infections in mice [abstract]. Federation of American Societies for Experimental Biology Conference. 20(4):A554.
Technical Abstract: Both selenium and vitamin E are important antioxidant nutrients. Previous studies have demonstrated that coxsackievirus B3 (CVB3) can rapidly select for more pathogenic variants in selenium or vitamin E deficient mice. It has been proposed that oxidative stress may lead to enhanced rates of viral evolution. Copper deficiency is also associated with increased levels of oxidative stress. Thus, we were interested in determining if copper deficiency would lead to enhanced virulence and pathology in mice infected with CVB3. Pregnant Swiss outbred mice were fed a copper deficient diet and received 30 µg/ml copper, as copper sulfate, in the drinking water. On the day the dams gave birth, one half of the dams were switched to drinking water without added copper. Mice were weaned at 3 weeks of age and maintained on a deficient copper diet with or without added copper to the water. At 4-5 weeks of age, the mice were infected with 105 TCID50 of coxsackievirus B3/20, a myocarditic strain, or B3/0, an amyocarditic strain. At seven days post-infection, copper deficient mice infected with the B3/20 virus had significantly elevated heart and pancreatic titers compared to mice fed an adequate diet. Heart pathology also was increased in copper deficient mice infected with either the B3/20 or B3/0 strains of coxsackievirus. Additional studies are being conducted to determine if the enhanced virulence and pathology is due to alterations in the host immune response and/or to the appearance of more pathogenic viral strains in the copper deficient mice.