Resistance to nucleoside analogs of selective mutants of human immunodeficiency virus type 2 reverse transcriptase.
AUTOR(ES)
Perach, M
RESUMO
We have studied selected mutants of human immunodeficiency virus type 2 (HIV-2) reverse transcriptase (RT) in a cell-free system in order to assess whether the mutant proteins exhibit a reduction in the sensitivity to nucleoside analog inhibitors similar to that of HIV-1 RT. We have modified, by site-directed mutagenesis, several of those amino acid residues so that their equivalent substitutions in HIV-1 RT have led to the formation of HIV-1 RT variants with the highest degree of resistance to dideoxynucleoside triphosphates (i.e., Glu-89-->Gly, Leu-74-->Val, and Ser-215-->Tyr [which is comparable to the Thr-215-->Tyr mutation of HIV-1 RT] and the double mutations Glu-89-->Gly/Ser-215-->Tyr and and Leu-74-->Val/Ser-215-->Tyr). The similarity found between resistance of the newly generated HIV-2 RT mutants to nucleoside analogs and that of the comparable mutants of HIV-1 RT can support the notion that the overall protein folding around the DNA polymerase active site in HIV-2 RT is quite similar to that of HIV-1 RT.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=188600Documentos Relacionados
- Action of uracil analogs on human immunodeficiency virus type 1 and its reverse transcriptase.
- PPi analogs as inhibitors of human T-lymphotropic virus type III reverse transcriptase.
- Substrate inhibition of the human immunodeficiency virus type 1 reverse transcriptase.
- Illimaquinone, a selective inhibitor of the RNase H activity of human immunodeficiency virus type 1 reverse transcriptase.
- Resistance to 2',3'-dideoxycytidine conferred by a mutation in codon 65 of the human immunodeficiency virus type 1 reverse transcriptase.