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Submitted to: Virology
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 6/8/2006 Publication Date: 7/24/2006 Citation: Smith, A.D., Dawson, H.D. 2006. Glutathione is required for efficient production of infectious picornavirus virions. Electronic Virology. Available: http://www.sciencedirect.com/ Interpretive Summary: Oxidative stress varies in different individuals and under different conditions; however antioxidants such as glutathione are produced to prevent oxidative stress from harming our health. Both diet and disease can affect how much glutathione is produced and some dugs such as buthionine sulfoximine (BSO) can inhibit cells from making glutathione. Glutathione has been reported to inhibit growth of viruses responsible for acquired immune deficiency disease, herpes and influenza; while cells treated with BSO increased growth of Sendai virus. We demonstrated that BSO can inhibit the growth of another class of viruses called the picornaviruses which include the virus that causes the common cold. The drug does not prevent the steps required for viral growth including production of the viral genetic code or viral proteins, but it does inhibit the virus from assembling new infectious virus. These results indicate that glutathione is important for picornavirus growth and could be used to enhance resistance against viruses that cause the colds. This work is important to those interested in enhancing human health through adequate nutrition and to scientists interested in the mechanism for control viral growth and disease. Technical Abstract: Glutathione is an intracellular reducing agent that helps maintain the redox potential of the cell and has been shown to be important for immune function. Glutathione levels can be influenced by diet and disease. Glutathione synthesis can be selectively inhibited by the drug, L-buthionine sulfoximine (BSO). Glutathione has been reported to inhibit replication of HIV, HSV-1, and influenza virus; while cells treated with BSO increased replication of Sendai virus. The role of glutathione in the replication of picornaviruses was found to be different. Pre-treatment of HeLa cell monolayers with BSO inhibited replication of CVB3, CVB4, and HRV14 with viral titers reduced by 6, 4, and 3 log10, respectively. The addition of glutathione ethyl ester, but not dithiothreitol or 2-mercaptoethanol, to the culture medium reversed the inhibitory effect of BSO in a dose dependent manner. Buthionine sulfoximine inhibited the CVB3 induced cytopathic effect (CPE) at low but not a high multiplicities of infection indicating that BSO treatment does not interfere with the mechanisms responsible for virally-induced CPE. Viral RNA and protein synthesis were not inhibited by BSO treatment. When virus concentrated by ultracentrifugation was examined by SDS-PAGE, it was observed that the normally expressed VP4 capsid protein was not present in preparations of virus propagated in cells treated with BSO. These results suggest that glutathione is important for production |
