Effect of antiviral agents on replication of herpes simplex virus type 1 in brain cultures.
An in vitro tissue culture system consisting of reaggregated embryonic brain cells was used to evaluate the inhibition of herpes simplex type 1 (HSV-1) by several antiviral compounds. The efficacy of acyclovir, vidarabine, bromovinyldeoxyuridine, and 9-(1,3-dihydroxy-2-propoxymethyl) guanine in HSV-1-infected Vero cell monolayer cultures was compared with that seen with brain cell aggregates. At a mean 50% inhibitory dose with Vero cells, acyclovir showed a 99% reduction of virus titer in brain cell aggregates. Vidarabine and 9-(1,3-dihydroxy-2-propoxymethyl) guanine gave a dose-dependent reduction in virus titer with Vero cells; however, in aggregate cultures treated with the same drugs a dose-dependent decrease at 24 h was followed by an increase to a point of no inhibition at 72 h postinfection. Pretreatment of brain cell aggregates with a hybrid human leukocyte interferon (Le IF-AD) reduced virus titers at 48 h postinfection but did not maintain this reduction at 72 h. In contrast, infected Vero cell monolayer cultures demonstrated a dose-dependent reduction in virus titers with Le IF-AD. Postinfection treatment with Le IF-AD did not reduce plaque formation in Vero cells but was effective in reducing virus titer in HSV-1-infected brain cell aggregates at 48 h postinfection. Antiviral concentrations of up to 200 micrograms or 200,000 IU/ml for interferon did not appear morphologically toxic to brain cells. Antiviral therapy of HSV-1-infected brain cell aggregates may more closely mimic in vivo responses than monolayer cultures.
D000212:Acyclovir / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001921:Brain / Q000382:microbiology*; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D015774:Ganciclovir; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects* / Q000502:physiology; D014709:Vero Cells; D014740:Vidarabine / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D007370:Interferon Type I; C020235:brivudine; D014740:Vidarabine; D001973:Bromodeoxyuridine; D015774:Ganciclovir; D000212:Acyclovir