In:
Antiviral Chemistry and Chemotherapy, SAGE Publications, Vol. 10, No. 6 ( 1999-12), p. 315-320
Abstract:
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, III B/2217RE/0.05 and III B/2217RE/0.25 , were two-and 15-fold resistant to RD4–2217, respectively, whereas III B/2217RE/1 and III B/2217RE/10 displayed 161-and 〉 238-fold resistance, respectively. Both III B/2217RE/1 and III B/2217RE/10 had 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 III B/2217RE/1 and III B/2217RE/10 appeared to be lower than that of wild-type III B in MT-4 cells, suggesting that the V189I plus T240I mutation may impair the enzymatic activity of HIV-1 RT.
Type of Medium:
Online Resource
ISSN:
2040-2066
,
2040-2066
DOI:
10.1177/095632029901000602
Language:
English
Publisher:
SAGE Publications
Publication Date:
1999
detail.hit.zdb_id:
2130088-4
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