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It has been recently shown that VP-16-213, a semi-synthetic derivative of podophyllotoxin, inhibits the function of mammalian DNA topoisomerase II. In the present study, we examined the effects of VP-16-213 on the replication of herpes simplex virus type 2 (HSV-2). The compound did not inhibit the synthesis of early viral polypeptides at concentrations at which viral DNA synthesis was strongly suppressed, but induced double-strand breaks in newly synthesized HSV DNA. Electron microscopic examination of treated cells revealed the presence of a number of capsids with empty or partial cores. The level of topoisomerase II activity remained unaltered after infection, and all attempts to isolate VP-16-213-resistant mutants of HSV-2 have failed in spite of extensive efforts. It is suggested therefore that the mode of action of VP-16-213 may be inhibition of viral DNA synthesis by impairing the function of host cell topoisomerase II.
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March 1975,
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Y Nishiyama, and
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Y Nishiyama, and
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Y Nishiyama, and
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Y Nishiyama, and
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Y Nishiyama, and
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March 1976,
Virology,
Y Nishiyama, and
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T Tsurumi, and
N Yamamoto, and
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K Shimokata
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Acta dermato-venereologica,
Y Nishiyama, and
H Fujioka, and
T Tsurumi, and
N Yamamoto, and
K Maeno, and
S Yoshida, and
K Shimokata
April 1973,
Virology,
