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Antimicrobial Agents and Chemotherapy, March 2004, p. 783-790, Vol. 48, No. 3
0066-4804/04/$08.00+0 DOI: 10.1128/AAC.48.3.783-790.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Departments of Pediatrics,1 of Microbiology and Immunology, Vanderbilt University School of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 372322
Received 2 January 2003/ Returned for modification 14 April 2003/ Accepted 30 October 2003
Zinc supplementation decreases the morbidity of lower respiratory tract infection in pediatric patients in the developing world. We sought to determine if zinc mediates a specific inhibitory effect against the major cause of pediatric lower respiratory tract disease, respiratory syncytial virus (RSV). We determined the in vitro inhibitory effect of three zinc salts (zinc acetate, lactate, and sulfate) on the replication of RSV at various concentrations of 10 and 1 mM and 100 and 10 µM. The degree of inhibition of RSV replication was examined in the presence of zinc during preincubation, adsorption, or penetration and was compared with that caused by salts of other divalent cations. Complete inhibition of RSV plaque formation was observed at 1 and 10 mM, representing reductions that were
106-fold. At the lowest concentration tested, 10 µM, we observed
1,000-fold reductions in RSV yield when zinc was present during preincubation, adsorption, penetration, or egress of virus. The therapeutic indices, determined as ratios of 50% toxicity concentration to 50% inhibitory concentration, were 100, 150, and 120 for zinc acetate, zinc lactate, and zinc sulfate, respectively. The inhibitory effect of zinc salts on RSV was concentration dependent and was not observed with other salts containing divalent cations such as calcium, magnesium, and manganese. RSV plaque formation was prevented by pretreatment of HEp-2 cell monolayer cultures with zinc or by addition of zinc to methylcellulose overlay media after infection. The results of this study suggest that zinc mediates antiviral activity on RSV by altering the ability of the cell to support RSV replication.
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