EVIDENCE FOR ANTIVIRAL ACTIVITY OF GLUTATHIONE - IN-VITRO INHIBITION OF HERPES-SIMPLEX VIRUS TYPE-1 REPLICATION

The role of glutathione (GSH) in the in vitro infection and replicatio n of human herpes simplex virus type 1 (HSV-1) was investigated. Intra cellular endogenous GSH levels dramatically decreased in the first 24 h after virus adsorption, starting immediately after virus challenge: The addition of exogenous GSH was not only able to restore its intrace llular levels almost up to those found in uninfected cells, but also t o inhibit > 99% the replication of HSV-1. This inhibition was concentr ation-dependent, not related to toxic effects on host cells and also m aintained if the exogenous GSH was added as late as 24 h after virus c hallenge, i.e. when virus infection was fully established. Electron mi croscopic examination of HSV-1-infected cells showed that GSH dramatic ally reduced the number of extracellular and intracytoplasmic virus pa rticles, whereas some complete nucleocapsids were still detected withi n the nuclei of GSH-treated cells. Consistent with this observation, i mmunoblot analysis showed that the expression of HSV-1-glycoprotein B, crucial for the release and the infectivity of virus particles, was s ignificantly decreased. Data suggest that exogenous GSH inhibits the r eplication of HSV-1 by interfering with very late stages of the virus life cycle, without affecting cellular metabolism.