title: (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) inhibits HIV-1 replication in epithelial cells, but not T-lymphocytes.
abstract: PMEA [9-(2-phosphonylmethoxyethyl)adenine] inhibited both HSV-1 and HIV-1 replication in MT-2 and HeLa-CD4 cells. (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine (HPMPC) inhibited both these viruses in the epithelioid HeLa-CD4 cells, but did not inhibit either virus in the T-lymphocytic MT-2 cells. PMEA and HPMPC are metabolized to their diphosphorylated 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, whereas HPMPCpp levels were approximately 3-10 fold lower in MT-2 cells, compared to HeLa-CD4 cells. These results indicate that HPMPC can inhibt HIV replication in the appropriate cell types, and show that differences in their metabolism cannot account entirely for the lack of antiviral efficacy of HPMPC in MT-2 cells.
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: R V
authors.initials: RV
authors.lastname: Srinivas
authors.forename: M
authors.initials: M
authors.lastname: Connely
authors.forename: A
authors.initials: A
authors.lastname: Fridland
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000378:metabolism / Q000494:pharmacology*; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology; D015704:CD4 Antigens / Q000235:genetics; D002460:Cell Line; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005818:Genetic Engineering; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000502:physiology; D006801:Humans; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation; D013601:T-Lymphocytes; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D015704:CD4 Antigens; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C053001:adefovir; D003596:Cytosine; D000225:Adenine; D000077404:Cidofovir