| Autor: |
Fujiwara, Masatoshi, Kodama, Eiichi N, Okamoto, Masayuki, Tokuhisa, Kenji, Ide, Teruhiko, Hanasaki, Yasuaki, Katsuura, Kimio, Takayama, Hiromitsu, Aimi, Norio, Mitsuya, Hiroaki, Shigeta, Shiro, Konno, Kenji, Yokota, Tomoyuki, Baba, Masanori |
| Zdroj: |
Antiviral Chemistry & Chemotherapy; December 1999, Vol. 10 Issue: 6 p315-320, 6p |
| Abstrakt: |
The non-nucleoside reverse transcriptase (RT) inhibitor RD4–2217 is a thiadiazole derivative that has proved to be a highly potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) replication in vitro. In this study we examined genotypic and phenotypic characteristics of RD4–2217-resistant mutants that have been obtained by serial passage of HIV-1 in MT-4 cells in the presence of increasing concentrations (0.05, 0.25, 1 and 10 μM) of the compound. The strains obtained, IIIB/2217RE/0.05and IIIB/2217RE/0.25, were two-and 15-fold resistant to RD4–2217, respectively, whereas IIIB/2217RE/1and IIIB/2217RE/10displayed 161-and >238-fold resistance, respectively. Both IIIB/2217RE/1and IIIB/2217RE/10had two amino acid substitutions, V189I and T240I, in the RT. Furthermore, RD4–2217 did not inhibit the replication of an HIV-1 molecular clone, which had the same mutation, at concentrations up to 10 μM, indicating that the V189I plus T240I mutation confers high-level resistance to RD4–2217. Interestingly, the replicability of IIIB/2217RE/1and IIIB/2217RE/10appeared to be lower than that of wild-type IIIBin MT-4 cells, suggesting that the V189I plus T240I mutation may impair the enzymatic activity of HIV-1 RT. |
| Databáze: |
Supplemental Index |
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