title: Effects of S-acetylglutathione in cell and animal model of herpes simplex virus type 1 infection.
abstract: Intracellular glutathione (GSH) plays an important regulatory role in the host response to viral infections. Replenishment of intracellular GSH is a desirable yet challenging goal, since systemic GSH supplementation is rather inefficient due to a short half-life of GSH in blood plasma. Further, GSH is not taken up by cells directly, but needs to be broken down into amino acids and resynthesized to GSH intracellularly, this process often being impaired during viral infections. These obstacles may be overcome by a novel glutathione derivative S-acetylglutathione (S-GSH), which is more stable in plasma and taken up directly by cells with subsequent conversion to GSH. In the present study, in vitro effects of supplementation with S-GSH or GSH on intracellular GSH levels, cell survival and replication of human herpes simplex virus type 1 (HSV-1) were studied in human foreskin fibroblasts. In addition, in vivo effects of supplementation with S-GSH or GSH on HSV-1-induced mortality were studied in hr/hr mice. In cell culture, viral infection resulted in a significant decrease of intracellular GSH levels. S-GSH efficiently and dose-dependently (5 and 10 mM tested) restored intracellular GSH, and this replenishment was more efficient than with GSH supplementation. In mice, S-GSH, but not GSH, significantly decreased HSV-1-induced mortality ( P<0.05). The data suggest that S-GSH is a suitable antiviral agent against HSV-1 both in vitro and in vivo, indicating that this drug may be of benefit in the adjunctive therapy of HSV-1 infections.
authors: Institute for Medical Virology, Johann Wolfgang Goethe University Hospital, Paul-Ehrlich Str. 40, 60596, Frankfurt am Main, Germany. j.vogel@em.uni-frankfurt.de
authors: Jens-Uwe
authors: JU
authors: Vogel
authors: Jaroslav
authors: J
authors: Cinatl
authors: Nurlan
authors: N
authors: Dauletbaev
authors: Sigune
authors: S
authors: Buxbaum
authors: Gernot
authors: G
authors: Treusch
authors: Jindrich
authors: J
authors: Cinatl
authors: Valentin
authors: V
authors: Gerein
authors: Hans Wilhelm
authors: HW
authors: Doerr
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D006561:Herpes Simplex / Q000188:drug therapy* / Q000401:mortality / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D008812:Mice, Hairless; D014709:Vero Cells / Q000378:metabolism / Q000821:virology; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; C096306:S-acetylglutathione; D005978:Glutathione