Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: January 9, 2005
Publication Date: April 1, 2005
Citation: Smith, A.D. 2005. Pretreatment of hela cells with the glutathione synthesis inhibitor, l-buthionine-sulfoximine (bso), inhibits replication of picornaviruses. Federation of American Societies for Experimental Biology Conference. 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 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 has not been studied. HeLa cell monolayers infected with coxsackievirus B3 (CVB3) at a low MOI (0.5-1.0) exhibited 100% cytopathic effect (CPE) by 24 hours but BSO-treated cell monolayers remained intact. In addition, there was an 8-log10 difference in viral titers observed between the untreated and BSOtreated cultures. Both untreated and BSO-treated HeLa cell monolayers infected with CVB3, CVB4, or HRV14 at a high MOI (5), exhibited equivalent levels of CPE indicating that BSO treatment did not interfere with the mechanisms responsible for virally-induced CPE but viral titers were reduced by 6, 4, and 4 log10, respectively. In contrast, the replication of another RNA virus, reovirus T1L, was unaffected by pretreatment of L-cells with BSO. Addition of glutathione reduced ethyl ester to BSO-treated monolayers restored replication of CVB3. These results suggest that glutathione plays an important role in picornavirus replication.