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Vitamin E Deficiency Intensifies the Myocardial Injury of Coxsackievirus B3 Infection of Mice^1,2,3,

Melinda A. Beck⁴, Peter C. Kolbeck^*, Lisa H. Rohr, Qing Shi, Virginia C. Morris and Orville A. Levander

Frank Porter Graham Child Development Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514-8180 ^* Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198 USDA, ARS, Beltsville Human Nutrition Research Center, Beltsville, MD 20705

Feeding a vitamin E-deficient diet increases pathology in hearts of mice infected with a myocarditic coxsackievirus B3 (CVB3/20). Hearts from infected mice fed a vitamin E-deficient diet rich in highly unsaturated fat (menhaden oil) exhibited more severe pathology than hearts from infected mice fed a vitamin E-deficient diet based largely on saturated fat (lard). Furthermore, a cloned and sequenced amyocarditic coxsackievirus B3 (CVB3/0), which caused little or no pathology in the hearts of vitamin E-supplemented mice, induced extensive cardiac pathology in vitamin E-deficient mice. In infected mice, both mitogen and antigen responses were depressed by vitamin E deficiency, although neutralizing antibody responses were unaffected. Natural killer cell responses were comparable in infected mice fed a lard-based diet with or without supplemented vitamin E. However, a menhaden oil-based diet, whether supplemented with vitamin E or not, significantly depressed natural killer cell activity in infected mice compared with mice fed the lard-based diet. Coxsackievirus B3/0 recovered from the heart of a vitamin E-deficient donor mouse, passaged one time onto HeLa cells, caused significant heart damage when passed back into vitamin E-supplemented recipient mice, demonstrating that the amyocarditic CVB3/0 had changed to a virulent phenotype. Enhanced virulence was also seen with CVB3/20 virus similarly passaged in a vitamin E-deficient donor. Our work demonstrates the important role of host nutritional antioxidant status in determining the severity of certain viral infections.

KEY WORDS: • coxsackievirus • Keshan disease • vitamin E • myocarditis • mice

¹ Presented in part at Experimental Biology 93, March 1993, New Orleans, LA [Beck, M. A., Morris, V. C. & Levander, O. A. (1993) Either selenium (Se) or vitamin E deficiency intensifies the myocardial injury of coxsackievirus B3 infection of mice. FASEB J. 7: A277 (abs.)].

² Supported in part by grants from the National Heart, Lung and Blood Institute (PHS 5-R29HL46195-04), National Institute of Child Health and Development (2-P30-HD03110-26), Center for Environmental Medicine and Lung Biology, UNC and The Frank Porter Graham Child Development Center, UNC (MAB).

³ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁴ To whom correspondence should be addressed.

Manuscript received 14 June 1993. Revision accepted 2 November 1993.

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