Modulators of Nucleotide Metabolism Inhibit HIV Replication in Lymphoid Cells and Affect Its Inhibition by Dideoxynucleosides

Abstract

Hydroxyurea (HU), - a ribonucleotide reductase inhibitor which depletes dNTP pools, inhibited HIV replication, and the extent of inhibition correlated with its antiproliferative effects. HU treatment, prior to, and during the initial 12 h of HIV infection, resulted in a significant reduction in virus yield, without affecting cell proliferation. AICA riboside, an IMP precursor which increases the flux of purine biosynthesis, also inhibited HIV replication suggesting a requirement for optimum ratios of the different dNTPs for efficient reverse transcription and virus replication. The different modulators also affected the antiviral efficacy of various dideoxynucleosides. HU enhanced the antiviral efficacy of both AZT and ddl, whereas AICA riboside potentiated ddl and did not exert any appreciable effect on AZT.