title: Antiviral effects of 6-diazo-5-oxo-L-norleucin on replication of herpes simplex virus type 1.
abstract: An L-glutamine antagonist, 6-diazo-5-oxo-L-norleucin (L-DON), inhibits replication of vesicular stomatitis virus, poliovirus and paramyxoviruses in cultured cells. We tested the antiviral activity of L-DON against different strains of herpes simplex virus type 1 (HSV-1) in Vero cells. In the presence of a physiological plasma concentration of L-glutamine (0.5mM) L-Don inhibited 50% production of virus plaques at concentrations ranging from 7.9 to 16 microM. At concentrations of 40 microM L-Don inhibited infectious virus yield by 99%. The antiviral activity of L-DON decreased with increasing L-glutamine concentrations. A concentration of 5000 microM of L-Don had no significant effects on the viability of Vero cells. Transmission electron microscopical investigations showed that L-DON prevented mainly envelopment of viral nucleocapsids in the cytoplasm. The immunoprecipitation experiments demonstrated selective inhibition of synthesis of HSV-1 glycoproteins in L-DON treated cells. The results showed that L-DON inhibits HSV-1 replication at a late stage in the virus replication cycle, probably the cytoplasmic maturation of virions and subsequent virion egress from the cells.
authors.affiliation: Department of Haematology and Oncology, J.W. Goethe-University, Frankfurt a.M., Germany.
authors.forename: J
authors.initials: J
authors.lastname: Cinatl
authors.forename: J U
authors.initials: JU
authors.lastname: Vogel
authors.forename: J
authors.initials: J
authors.lastname: Cinatl
authors.forename: H
authors.initials: H
authors.lastname: Kabickova
authors.forename: B
authors.initials: B
authors.lastname: Kornhuber
authors.forename: H W
authors.initials: HW
authors.lastname: Doerr
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D003980:Diazooxonorleucine / Q000494:pharmacology*; D005973:Glutamine / Q000494:pharmacology; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D014709:Vero Cells / Q000187:drug effects; D014759:Viral Envelope Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1; C044768:glycoprotein E, herpes simplex virus type 1; D003980:Diazooxonorleucine; D005973:Glutamine