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Title: Glutathione is required for efficient production of infectious picornavirus virions

Glutathione is an intracellular reducing agent that helps maintain the redox potential of the cell and is important for immune function. The drug L-buthionine sulfoximine (BSO) selectively inhibits glutathione synthesis. Glutathione has been reported to block replication of HIV, HSV-1, and influenza virus, whereas cells treated with BSO exhibit increased replication of Sendai virus. Pre-treatment of HeLa cell monolayers with BSO inhibited replication of CVB3, CVB4, and HRV14 with viral titers reduced by approximately 6, 5, and 3 log{sub 1}, respectively. The addition of glutathione ethyl ester, but not dithiothreitol or 2-mercaptoethanol, to the culture medium reversed the inhibitory effect of BSO. Viral RNA and protein synthesis were not inhibited by BSO treatment. Fractionation of lysates from CVB3-infected BSO-treated cells on cesium chloride and sucrose gradients revealed that empty capsids but not mature virions were being produced. The levels of the 5S and 14S assembly intermediates, however, were not affected by BSO treatment. These results demonstrate that glutathione is important for production of mature infectious picornavirus virions.
Authors:
 [1] ;  [2]
  1. Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705 (United States). E-mail: smitha@ba.ars.usda.gov
  2. Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705 (United States). E-mail: dawsonh@ba.ars.usda.gov
Publication Date:
OSTI Identifier:
20850562
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 353; Journal Issue: 2; Other Information: DOI: 10.1016/j.virol.2006.06.012; PII: S0042-6822(06)00407-7; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AIDS VIRUS; CESIUM CHLORIDES; CULTURE MEDIA; ESTERS; GLUTATHIONE; HELA CELLS; INFLUENZA VIRUSES; REDOX POTENTIAL; REDUCING AGENTS; RNA; SACCHAROSE; SYNTHESIS