MODULATORS OF NUCLEOTIDE-METABOLISM INHIBIT HIV REPLICATION IN LYMPHOID-CELLS AND AFFECT ITS INHIBITION BY DIDEOXYNUCLEOSIDES

Hydroxyurea (HU), - a ribonucleotide reductase inhibitor which deplete s dNTP pools, inhibited HIV replication, and the extent of inhibition correlated with its antiproliferative effects. HU treatement, prior to , and during the initial 12 h of HIV infection, resulted in a signific ant reduction in virus yield, without affecting cell proliferation. AI CA riboside, an IMP precursor which increases the flux of purine biosy nthesis, also inhibited HIV replication suggesting a requirement for o ptimum ratios of the different dNTPs for efficient reverse transcripti on and virus replication. The different modulators also affected the a ntiviral efficacy of various dideoxynucleosides. HU enhanced the antiv iral efficacy of both AZT and ddl, whereas AICA riboside potentiated d dl and did not exert any appreciable effect on AZT.