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Copyright 0 1973 American Society for Microbiology Printed in U.S.A.
inhibition of vaccinia growth at 4 ug/na]. It was lung cells with two well-known inhibitors of
not active against adenovirus type ;i. In the DNA synthesis: 5-iodo-2-deoxyuridine (IUdR)
same test system, it showed no activitiy against and cytosine arabinoside (CA). The results (Fig.
rhinovirus type 2 or coronavirus type 229E. In 2) show that aphidicolin, like IUdR and CA, is a
confluent primary calf kidney cultures, powerful inhibitor of cellular DNA synthesis.
aphidicolin was not active against infltienza AO, None of the compounds had any effect on
A,, or A2, or parainfluenza type 1. cellular RNA synthesis at 12.5 jg/ml, the high-
Mode of action. The specific inhi ,bition of est concentration tested. Parallel cultures were
DNA viruses by aphidicolin suggested that the infected with approximately 100 TCD,. of
antibiotic is an inhibitor of DNA syntiiesis. We herpes simplex type 1, treated with the same
therefore compared the effects of aphidlicolin on range of concentrations of IUdR, CA, or
the nucleic acid synthesis of culture'd human aphidicolin, and harvested 24 h later to measure
virus yields.
It is clear that aphidicolin depresses virus
H17 yield and cellular DNA synthesis in parallel,
and it is therefore probable that it exerts its
antiviral effects by inhibiting herpes virus DNA
pH synthesis. IUdR, on the other hand, is antiviral
at concentrations much lower than those which
inhibit cellular DNA synthesis, suggesting a
considerable degree of specificity of IUdR for
c
75-
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75- .iI
II
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._
I
U
50-
II I.
50-
4rIi Ii
at
e Virus&4-d~~~~~~~
Il
. . . . .
25- 25- D.N.A4 |
D.N.A_-
Virus6-
I I I
125 31 0:8 0'2 0.b50.6125 12.5 3:1 0:8 0:2 650.01125 1d.5 3:1 0:8 0;2 0.05 0.0125
big/ml iggml ug/ml
FIG. 2. Effect of aphidicolin, IUdR, and CA on RNA (0) and DNA (0) synthesis of uninfected human
embryonic lung cells, and on the growth of herpes simplex type 1 (A) in infected cells. All results are expressed
as a percentage of appropriate controls for ease of comparison.
296 BUCKNALL ET AL. ANTIMICROB. AG. CHEMOTHER.
was somewhat less effective against an ocular
challenge of 400 eye mean infective dose (ID50)
than was IUdR at 1 mg/ml (Fig. 3). By increas-
ing the concentration of aphidicolin to 10 mg/
ml, or by reducing the challenge virus to 40 eye ' bControl