Protective effect of the acyclic nucleoside phosphonate tenofovir toward human T-cell leukemia/lymphotropic virus type 1 infection of human peripheral blood mononuclear cells in vitro.
9-(R)-[(2-Phosphonomethoxy)propyls]adenine (tenofovir), is an acyclic nucleoside phosphonate known to inhibit HIV replication in vitro and to reduce viremia in HIV-infected patients. Here we have investigated whether tenofovir is able to protect peripheral blood mononuclear cells (PBMCs) from healthy donors against human T-cell leukemia/lymphotropic virus type 1 (HTLV-1) infection in vitro. PBMCs were pre-treated with tenofovir and infected by exposure to an irradiated cell line chronically harbouring HTLV-1. Measurements of viral DNA, as well as viral gene and protein expression, at 4 weeks after infection, revealed that tenofovir at concentrations of 1 microM and higher completely protected PBMCs against HTLV-1; lower concentrations did not fully prevent HTLV-1 infection of the cultures. Nevertheless, in the long term, cell growth of infected PBMCs was inhibited in vitro even by 0.1 microM tenofovir. In addition, tenofovir directly inhibited HTLV-1 reverse transcriptase activity, in a cell-free assay that utilizes a crude preparation from HTLV-1 viral particles as a source of the enzyme. The selectivity index of tenofovir for HTLV-1, was about four times higher than that of azidothymidine. Taken together our results strongly encourage further studies to investigate the real impact of tenofovir towards HTLV-1 infection.
Balestrieri
Emanuela
E
Department of Neuroscience, University of Rome Tor Vergata, Via Montpellier 1, 00135 Rome, Italy.
Sciortino
Maria Teresa
MT
Mastino
Antonio
A
Macchi
Beatrice
B
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000494:pharmacology*; D004279:DNA, Viral / Q000032:analysis; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D015458:Leukemia, T-Cell / Q000188:drug therapy; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology*; D063065:Organophosphonates / Q000494:pharmacology*; D000068698:Tenofovir
D019380:Anti-HIV Agents; D004279:DNA, Viral; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine