S)-1-(3-HYDROXY-2-PHOSPHONYLMETHOXYPROPYL)CYTOSINE (HPMPC) INHIBITS HIV-1 REPLICATION IN EPITHELIAL-CELLS, BUT NOT T-LYMPHOCYTES

PMEA [9-(2-phosphonylmethoxyethyl)adenine] inhibited both HSV-1 and HI V-1 replication in MT-2 and HeLa-CD4 cells. -1-[3-hydroxy-2-(phosphony lmethoxy)propyl]cytosine (HPMPC) inhibited both these viruses in the e pithelioid HeLa-CD4 cells, but did not inhibit either virus in the T-l ymphocytic MT-2 cells. PMEA and HPMPC are metabolized to their diphosp horylated forms within cells, which then inhibit viral polymerases. We therefore compared the metabolism of PMEA and HPMPC in MT-2 and HeLa- CD4 cells. PMEApp formation was efficient in both the cell types, wher eas HPMPCpp levels were similar to 3-10 fold lower in MT-2 cells, comp ared to HeLa-CD4 cells. These results indicate that HPMPC can inhibt H IV replication in the appropriate cell types, and show that difference s in their metabolism cannot account entirely for the lack of antivira l efficacy of HPMPC in MT-2 cells. (C) 1997 Elsevier Science B.V.