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Enhanced in vitro Reactivation of Herpes Simplex Virus Type 2 from Latently Infected Guinea-pig Neural Tissues by 5-Azacytidine

The Division of Infectious Diseases, Children's Hospital Research Foundation and The James N. Gamble Institute of Medical Research, 2141 Auburn Avenue, Cincinnati, Ohio 45219, U.S.A.

5-Azacytidine (5-AZC) reduces cytosine methylation in DNA and has been reported to activate quiescent virus genes. Treatment of explant cultures of latently herpes simplex virus type 2 (HSV-2)-infected guinea-pig dorsal root ganglia and spinal cords in vitro with 5-AZC significantly enhanced the rate of HSV recovery. Both the number of isolates from ganglia (P < 0.001) and the rate of recovery (P < 0.001) were significantly increased with the addition of 50 µM-5-AZC to explant cultures. Increased virus recovery appeared to be due to the induction of reactivation of latent virus, rather than an increase in replication, since 5-AZC inhibited HSV replication. These data support a role for methylation in HSV latency and reactivation.

Keywords: HSV-2, latency, methylation, 5-azacytidine

Received 5 October 1987; accepted 12 February 1988.

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