Effect of acyclovir [9-(2-hydroxyethoxymethyl)guanine] on Epstein-Barr virus DNA replication.
The effect of acyclovir [9-(2-hydroxyethoxymethyl)guanine] on Epstein-Barr virus (EBV) DNA replication in the lymphoblastoid cell lines P3HR-1 and Raji is reported. Acyclovir at a concentration of 100 microM completely inhibited EBV DNA synthesis in superinfected Raji cells, but did not inhibit DNA synthesis in mock-infected cells. The number of EBV genome equivalents per cell in the virus-producing cell line P3HR-1 was significantly reduced by acyclovir, whereas the number of latent EBV genomes in Raji cells was not affected by the drug. In situ cytohybridization performed on untreated P3HR-1 cultures revealed the presence of relatively large amounts of EBV DNA in 15 to 20% of the cells. After a 100 microM drug treatment, no P3HR-1 cells contained levels of EBV DNA detectable by in situ cytohybridization. Indirect immunofluorescence studies demonstrated that during treatment with 100 microM acyclovir for 7 days, the percentage of P3HR-1 cells expressing viral capsid antigen was reduced. The EBV DNA remaining in P3HR-1 cells after treatment with 100 microM acyclovir (approximately 14 genomes per cell) had the properties of covalently closed circular DNA with an average molecular weight of 108 X 10(6), as determined by contour length measurements.
D000212:Acyclovir; D000956:Antigens, Viral; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D004279:DNA, Viral / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005814:Genes, Viral / Q000187:drug effects; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology; D006801:Humans; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization
D000956:Antigens, Viral; D004279:DNA, Viral; D006147:Guanine; D004247:DNA; D000212:Acyclovir