Inhibition of urethane leukaemia virus, a murine retrovirus, in mice by zidovudine.
The purpose of the study was to characterize in vivo an immunodepressive murine retroviral 'model' for the possible testing of drugs against HIV infection. Urethane leukaemia virus (ULV) injected into adult BALB/c mice (10(5) focus-forming units/mouse) caused a small, significant splenomegaly from 2 to at least 9 weeks after virus inoculation. Virus was also present in up to 60% nucleated splenocytes (XC 'infectious centre assay'). Effects on splenomegaly and virus in splenocytes were assayed following various regimens of zidovudine given as 0.5 mg/ml or 0.25 mg/ml in drinking water. Regimens included continuous treatment both before and after ULV, only before, and only after ULV inoculation. Zidovudine was also given for a limited period immediately after virus, or initiated after virus infection was established. Zidovudine given continuously at and following ULV infection completely prevented splenomegaly and virus expression in splenocytes. No other regimen was as effective; however, limited zidovudine treatment immediately after virus inoculation greatly reduced the effects of virus, while the same dose initiated after virus infection was established had only a small ameliorating effect. We conclude that ULV may prove to be a useful addition to other available murine systems, and this is discussed.
Harvey
J J
JJ
Division of Sexually Transmitted Diseases, MRC Clinical Research Centre, Harrow, UK.
Tuffrey
M
M
Wedderburn
N
N
Alexander
F
F
Curtis
J
J
Taylor-Robinson
D
D
Doré
C
C
D000704:Analysis of Variance; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size / Q000187:drug effects; D012190:Retroviridae / Q000187:drug effects* / Q000472:pathogenicity; D013154:Spleen / Q000033:anatomy & histology; D013163:Splenomegaly / Q000188:drug therapy; D010948:Viral Plaque Assay; D015215:Zidovudine / Q000494:pharmacology*
D015215:Zidovudine