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Effects of Certain Nucleoside Analogues on Human Cytomegalovirus Replication in vitro

¹ Cancer Research Center
and² Departments of Pharmacology
³ Departments of Microbiology and Immunology
and⁴ Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514
and⁵ Laboratory of Organic Chemistry, Sloan-Kettering Institute for Cancer Research, Rye, New York 10580, U.S.A.

Four nucleoside analogues, 1-(2'-deoxy-2'-fluoro--D-arabinofuranosyl)-5-methyluracil(FMAU), -5-iodouracil (FIAU), -5-methylcytosine (FMAC) and -5-iodocytosine (FIAC), were studied for their effect on human cytomegalovirus (HCMV) replication in vitro. FMAU, FIAU, FMAC and FIAC showed antiviral activities for four strains of HCMV (Major, Clegg, D₅₅₀ and Towne) in a plaque reduction asssay, with a dose required for 50% inhibition (ED₅₀) in the range of 0.1 to 0.65 µM. At a concentration of 1 µM-FMAU or -FIAC, the synthesis of five virus-specific late polypeptides of molecular weights 150000, 120000, 67000, 54000 and 27000 was entirely blocked. Quantification of Towne viral DNA synthesis, using complementary RNA-DNA hybridization with a Towne-specific cRNA probe, demonstrated a complete inhibition of HCMV DNA replication at 1 µM of FMAU or FIAC. After the removal of the inhibitors, however, viral DNA synthesis resumed, and infectious virus reappeared, indicating that the inhibition of HCMV replication by these nucleoside analogues was of a virostatic reversible type.

Keywords: CMV, nucleoside analogues, inhibition

Received 14 April 1983; accepted 14 September 1983.