A Quantitative Study of the Effects of Several Nucleoside Analogues on Established Herpes Encephalitis in Mice

Abstract

SUMMARYMice with established herpes encephalitis were used to compare the effects of chemotherapy using three different nucleoside analogues. Encephalitis was produced by intranasal inoculation of a type 1 strain of herpes simplex virus. Without chemotherapy all mice died within 5 to 7 days of inoculation. Oral acyclovir (ACV) was a successful preventative measure if commenced within 2 days of inoculation but much less effective if the onset of treatment was further delayed. From the third day, when central nervous system infection had definitely become established, ACV only reduced mortality if given intraperitoneally (i.p.) at regular 6-hourly intervals. Comparison with bromovinyldeoxyuridine (BVdU) and the new nucleoside analogue dihydroxypropoxymethylguanine (DHPG) using the same 6-hourly i.p. regimen revealed that BVdU was poorly effective, despite better activity in vitro, whereas DHPG was the most successful. Virus was rapidly eradicated from all parts of the brain by DHPG therapy, and by day 10, no infectious virus remained in the brains of treated mice, no virus antigens were observed and no trace of virus DNA could be detected in neural tissues by Southern blotting.

Potent In Vivo Antiviral Activity of the Herpes Simplex Virus Primase-Helicase Inhibitor BAY 57-1293

“…The reduced efficacy of famciclovir against HSV-2 compared with that against HSV-1, as also apparent from our data, however, is in accordance with results obtained in in vitro plaque reduction assays (8). The poor oral activity of brivudine, despite its strong in vitro activity against HSV-1, has also been described previously (9). The failure of brivudine in the HSV-2 lethal challenge model is reflected by its poor in vitro activity against HSV-2.…”

“…The ED 50 s published in the literature vary according to the model and treatment regimen used. The superiority of ganciclovir over acyclovir, as evident from our work, is well documented in various murine models in the literature (3,9,11). The activity of valacyclovir versus that of famciclovir has been a matter of debate (21), with a superiority of famciclovir being seen by some (20) but not by others (12).…”

“…The activities of orally administered BAY 57-1293 for the treatment of acute HSV-1 and HSV-2 infections were assessed in a murine lethal challenge model of disseminated herpes, including herpes encephalitis. This model is widely used for the evaluation of antiviral agents (4,9). Mice were infected intranasally and were treated 6 h later with the compounds under evaluation for 5 consecutive days three times a day (t.i.d.).…”

Effect of antiviral agents on replication of herpes simplex virus type 1 in brain cultures

“…In a mouse model of HSV encephalitis, DHPG was found to be more successful than ACV or BVDU in eradicating HSV from infected brain (12 6. Effect of postinfection treatment with interferon on the replication of virus in HSV-1-infected aggregates.…”

Herpes Simplex Virus Type 2 Latency in the Footpad of Mice: Effect of Acycloguanosine on the Recovery of Virus

“…To date all examined isolates were found to be ACG-sensitive. The efficacy of ACG in eradicating infectious HSV in acutely infected mice has been widely reported by other workers (Kerren et al, 1982;Field et al, 1984). However to ascertain that ACG is also effective in inhibiting HSV-2 replication in the mouse FP, acutely infected mice were treated with ACG either in the drinking water or by an i.p.…”