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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Characterization of human immunodeficiency virus type 1 strains resistant to the non-nucleoside reverse transcriptase inhibitor RD4-2217.

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 microM) 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, V1891 and T2401, 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 microM, indicating that the V1891 plus T2401 mutation confers high-level resistance to RD4-2217. Interestingly, the replicability of III(B2217RE/1) and III(B/2217RE/10) appeared to be lower than that of wildtype III(B) in MT-4 cells, suggesting that the V1891 plus T2401 mutation may impair the enzymatic activity of HIV-1 RT.[1]

References

  1. Characterization of human immunodeficiency virus type 1 strains resistant to the non-nucleoside reverse transcriptase inhibitor RD4-2217. Fujiwara, M., Kodama, E.N., Okamoto, M., Tokuhisa, K., Ide, T., Hanasaki, Y., Katsuura, K., Takayama, H., Aimi, N., Mitsuya, H., Shigeta, S., Konno, K., Yokota, T., Baba, M. Antivir. Chem. Chemother. (1999) [Pubmed]
 
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