Efficacy of dideoxynucleosides against human foamy virus and relationship to its reverse transcriptase amino acid sequence and structure.
Human foamy virus (HFV), a retrovirus of simian origin which occasionally infects humans, is the basis of retroviral vectors in development for gene therapy. Clinical considerations of how to treat patients developing an uncontrolled infection by either HFV or HFV-based vectors need to be raised. We determined the susceptibility of the HFV to dideoxynucleosides and found that only zidovudine was equally efficient against the replication of human immunodeficiency virus type 1 (HIV-1) and HFV. By contrast, zalcitabine (ddC), lamivudine (3TC), stavudine (d4T), and didanosine (ddI) were 3-, 3-, 30-, and 46-fold less efficient against HFV than against HIV-1, respectively. Some amino acid residues known to be involved in HIV-1 resistance to ddC, 3TC, d4T, and ddI were found at homologous positions of HFV reverse transcriptase (RT). These critical amino acids are located at the same positions in the three-dimensional structure of HIV-1 and HFV RT, suggesting that both enzymes share common patterns of inhibition.
Yvon-Groussin
A
A
Department of Virology, UPRES EA 2387, Pitié-Salpêtrière Hospital, Paris, France.
Mugnier
P
P
Bertin
P
P
Grandadam
M
M
Agut
H
H
Huraux
J M
JM
Calvez
V
V
D000998:Antiviral Agents / Q000494:pharmacology*; D015224:Dideoxynucleosides / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry / Q000187:drug effects*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D020539:Sequence Analysis, Protein; D016092:Spumavirus / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase