EFFECT OF GOLD (I) COMPOUNDS ON THE VIRULENCE OF AN AMYOCORDITIC STRAIN OF COXSACKIEVIRUS

Authors: Smith, Allen; SOUTH, PAUL - FORMERLY OF USDA; Levander, Orville

Submitted to: Biological Trace Element Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/7/2001
Publication Date: 12/1/2001
Citation: Smith, A.D., South, P.K., Levander, O.A. 2001. Effect of gold (i) compounds on the virulence of an amyocorditic strain of coxsackievirus. Biological Trace Element Research.

Interpretive Summary: Selenium is an important mineral nutrient that is present in some proteins of the cell that are important for protecting our bodies from oxidative stress. Compounds that contain gold have a high affinity for proteins that contain selenium. Coxsackieviruses can cause heart muscle disease in humans. In mice deficient in selenium, coxsackieviruses that normally do not cause disease change to a form of the virus that does cause heart muscle disease. This paper investigates how gold-containing compounds, which can act as selenium antagonists, affect a coxsackievirus infection. Two gold compounds were studied, aurothioglucose and aurothiomalate. Aurothiomalate, but not aurothioglucose caused increased mortality in infected mice. In addition, aurothiomalate caused increased heart and pancreatic damage in coxsackievirus infected mice. The virus grew better in and was not cleared from gold-treated mice as quickly as untreated mice. Both gold compounds inhibit the action of one but not another selenium-containing protein important for protecting our bodies from oxidative stress. However, only aurothiomalate increased the severity of the virus induced disease. This indicates that the aurothiomalate is probably not causing its effect by interfering with the normal actions of selenium. Instead, the compound may exert its effect by altering the immune response of the mice to the virus.

Technical Abstract: Coxsackieviruses, especially B strains (CVB), are known etiological agents of myocarditis. Both amyocardititc and myocarditic strains exist and at least one amyocarditic strain, CVB3/0, can convert to virulence when passaged through selenium or vitamin E deficient mice. Gold (I)- containing compounds, such as aurothiomalate (ATM) and aurothioglucose (ATG), can act as selenium antagonists. In this study, we examined the effect of intraperitoneal administration of equal doses of ATM or ATG on the virulence of CVB3/0. ATM but not ATG increased mortality in CVB3/0 infected mice. CVB3/0 infected mice treated with ATM had total necrosis of the pancreatic exocrine tissue. Heart damage also occurred in ATM- treated mice but did not correlate with mortality. Increased viral titers and persistence were observed in ATM- and to a lesser extent, ATG-treated mice. Thus, under our conditions, ATM increased the virulence of CVB3/0 whereas ATG did not. ATG and ATM inhibited thioredoxin reductase but not glutathione peroxidase activities in heart and pancreas. In contrast, selenium deficiency reduces both enzyme activities. Thus, it is unlikely that these compounds affect virulence by acting as selenium antagonists.