Copper deficiency increases the virulence of amyocarditic and myocarditic strains of coxsackievirus B3 in mice.
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 whether a copper deficiency would similarly alter the pathogenesis of CVB3 infections, Swiss outbred dams and their litters were fed copper-deficient diets from birth and received either deionized water or water with 0.315 mmol/L copper as copper sulfate. At 4 wk of age, copper-adequate or -deficient male and female offspring were infected with an amyocarditic or myocarditic strain of CVB3. Heart titers were elevated at d 3 and 7 postinfection in copper-deficient mice infected with the myocarditic CVB3 strain (CVB3/20) but only at d 7 in deficient mice infected with the amyocarditic CVB3 strain (CVB3/0) compared with copper-adequate controls. Copper-deficient mice infected with either strain of CVB3 had increased cardiac pathology compared with copper-adequate controls. Genomic sequences of viruses isolated from copper-adequate and -deficient mice were identical. Heart cytokine expression was elevated in copper-deficient CVB3-infected mice compared with 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, presumably due to increased viral load.
Smith
Allen D
AD
Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, USDA, Beltsville, MD 20705, USA. allen.smith@ars.usda.gov
Botero
Sebastian
S
Levander
Orville A
OA
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003300:Copper / Q000172:deficiency*; D003384:Coxsackievirus Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000235:genetics; D029822:Enterovirus B, Human / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D005260:Female; D006321:Heart / Q000821:virology; D007109:Immunity; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D051379:Mice; D009205:Myocarditis / Q000821:virology*; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis
D000914:Antibodies, Viral; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012333:RNA, Messenger; D003300:Copper