A method for evaluating antiviral drug susceptibility of Epstein-Barr virus
Charlotte A Romain1, Henry H Balfour Jr1,2, Heather E Vezina1,3, Carol J Holman1
1Department of Laboratory Medicine and Pathology, 2Department of Pediatrics, 3Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA
Abstract: We developed an in vitro Epstein-Barr virus (EBV) drug susceptibility assay using P3HR1 cells or lymphoblastoid cells from subjects with infectious mononucleosis, which were grown in the presence of various concentrations of acyclovir (ACV), ganciclovir (GCV) or R-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine (H2G) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA). On day 7, total cellular DNA was extracted and EBV DNA was detected using an in-house quantitative real-time polymerase chain reaction (PCR) method. All three drugs had in vitro activity against EBV in both the laboratory standard producer cell line P3HR1 and in subject-derived lymphoblastoid cell lines. The median 50% inhibitory concentrations (IC50s) in P3HR1 cells were: ACV, 3.4 μM; GCV, 2.6 μM; and H2G, 2.7 μM and in 3 subject-derived cells were: ACV, 2.5 μM; GCV, 1.7 μM; and H2G, 1.9 μM. Our assay can be used to screen candidate anti-EBV drugs. Because we can measure the IC50 of patients’ strains of EBV, this assay may also be useful for monitoring viral resistance especially in immunocompomised hosts receiving antiviral drugs for prevention or treatment of EBV diseases.
Keywords: Epstein-Barr virus, ganciclovir, acyclovir, valomaciclovir, H2G, antivirals
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