Effect of acyclovir [9-(2-hydroxyethoxymethyl)guanine] on Epstein-Barr virus DNA replication

Abstract

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.

Use of Fractional Factorial Designs in Antiviral Drug Studies

“…We further observe strong interaction between D and E, and possibly significant interactions among A, B, and C. Note that A, B, and C are Interferon drugs that are cytokines derived from immune system, 22 while D and E are chemical drugs designed more specific to work at DNA and RNA level. 23,24 The data suggest that the interactions within both Interferon group and chemical drug group are significant, which agrees with published reports from clinical trials. 25,26 However, no significant interactions between Interferon group and Ribavirin/Acyclovir are observed, indicating distinct antiviral pathways between these two drug categories.…”

The Role of Antiviral Prophylaxis for the Prevention of Epstein–Barr Virus–Associated Posttransplant Lymphoproliferative Disease in Solid Organ Transplant Recipients: A Systematic Review

“…EBV encodes a thymidine kinase (TK) enzyme that can convert nucleoside analogs to their monophosphate form, which is then converted by cellular enzymes to biologically active triphosphates that target viral DNA polymerase resulting in apoptosis and death of infected cells . Studies have shown that acyclovir, valacyclovir and ganciclovir have an inhibitory effect on lytic EBV DNA replication in vitro , but proliferating cells with EBV infection are transformed B cells that have not undergone lytic viral infection; therefore, and none of these antiviral agents can act on these EBV‐driven proliferations in vitro or on the latently infected B cells that do not express the EBV‐TK proteins . Perhaps the use of antiviral prophylaxis in high‐risk D+/R− patients would prevent primary infection at the time of transplant; in fact, lytic EBV replication may play an important role in primary EBV infection .…”

Lymphomas following cardiac transplantation. Case report and review of the literature

“…The proported role that the EBV plays in the pathogenesis of post-transplant lymphoproliferative disorders has led investigators to believe that the antiviral agent, acyclovir, may be a useful treatment for this disorder. Acyclovir works through inhibition of EBV DNApolymerase, thereby suppressing linear EBV DNA synthesis and the number of cells producing the virus [30]. Cells that latently carry the circular viral genome are not affected, nor is CMV, itself immunosuppressive to the host.…”