title: Resistance to nucleoside analogs of selective mutants of human immunodeficiency virus type 2 reverse transcriptase.
abstract: 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.
authors.affiliation: Department of Cell Biology and Histology, Sickler School of Medicine, Tel Aviv University, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Perach
authors.forename: T
authors.initials: T
authors.lastname: Rubinek
authors.forename: A
authors.initials: A
authors.lastname: Hizi
mesh_terms: D000596:Amino Acids / Q000235:genetics; D000998:Antiviral Agents / Q000494:pharmacology*; D002474:Cell-Free System; D054303:HIV Reverse Transcriptase; D015498:HIV-2 / Q000187:drug effects / Q000201:enzymology*; D016297:Mutagenesis, Site-Directed; D009705:Nucleosides / Q000494:pharmacology*; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors
chemical_list: D000596:Amino Acids; D000998:Antiviral Agents; D009705:Nucleosides; D018894:Reverse Transcriptase Inhibitors; C072416:reverse transcriptase, Human immunodeficiency virus 2; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase