A novel mutation (F227L) arises in the reverse transcriptase of human immunodeficiency virus type 1 on dose-escalating treatment of HIV type 1-infected cell cultures with the nonnucleoside reverse transcriptase inhibitor thiocarboxanilide UC-781.
Treatment of wild-type human immunodeficiency virus [HIV-1(IIIB)]-infected cell cultures with the thiocarboxanilide UC-781 under low selective pressure (i.e., 0.01 microg/ml) resulted in the emergence of V106A RT mutant virus. On increasing drug concentrations (stepwise up to 30 microg/ml) the virus...
| Main Authors: | , , , |
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| 格式: | Journal article |
| 語言: | English |
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1998
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| _version_ | 1826285178467647488 |
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| author | Balzarini, J Pelemans, H Esnouf, R De Clercq, E |
| author_facet | Balzarini, J Pelemans, H Esnouf, R De Clercq, E |
| author_sort | Balzarini, J |
| collection | OXFORD |
| description | Treatment of wild-type human immunodeficiency virus [HIV-1(IIIB)]-infected cell cultures with the thiocarboxanilide UC-781 under low selective pressure (i.e., 0.01 microg/ml) resulted in the emergence of V106A RT mutant virus. On increasing drug concentrations (stepwise up to 30 microg/ml) the virus retained the V106A RT mutation but acquired the novel F227L mutation in the RT genome in addition to the L100I, K1O1I, and Y181C mutations. This multiple-mutant virus proved highly resistant to virtually all nonnucleoside RT inhibitors (NNRTIs) (e.g., nevirapine, delavirdine, and loviride), but retained full sensitivity to nucleoside analogs such as AZT, ddI, (-)FTC, and 3TC. The F227 amino acid is highly conserved in HIV-1 strains and forms part of the NNRTI-binding pocket. Our model suggests a hydrophobic interaction between F227 and the chloro atom of UC-781. |
| first_indexed | 2024-03-07T01:24:57Z |
| format | Journal article |
| id | oxford-uuid:91a72474-f00d-4ebd-9e4b-94d2238e8583 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:24:57Z |
| publishDate | 1998 |
| record_format | dspace |
| spelling | oxford-uuid:91a72474-f00d-4ebd-9e4b-94d2238e85832022-03-26T23:20:09ZA novel mutation (F227L) arises in the reverse transcriptase of human immunodeficiency virus type 1 on dose-escalating treatment of HIV type 1-infected cell cultures with the nonnucleoside reverse transcriptase inhibitor thiocarboxanilide UC-781.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:91a72474-f00d-4ebd-9e4b-94d2238e8583EnglishSymplectic Elements at Oxford1998Balzarini, JPelemans, HEsnouf, RDe Clercq, ETreatment of wild-type human immunodeficiency virus [HIV-1(IIIB)]-infected cell cultures with the thiocarboxanilide UC-781 under low selective pressure (i.e., 0.01 microg/ml) resulted in the emergence of V106A RT mutant virus. On increasing drug concentrations (stepwise up to 30 microg/ml) the virus retained the V106A RT mutation but acquired the novel F227L mutation in the RT genome in addition to the L100I, K1O1I, and Y181C mutations. This multiple-mutant virus proved highly resistant to virtually all nonnucleoside RT inhibitors (NNRTIs) (e.g., nevirapine, delavirdine, and loviride), but retained full sensitivity to nucleoside analogs such as AZT, ddI, (-)FTC, and 3TC. The F227 amino acid is highly conserved in HIV-1 strains and forms part of the NNRTI-binding pocket. Our model suggests a hydrophobic interaction between F227 and the chloro atom of UC-781. |
| spellingShingle | Balzarini, J Pelemans, H Esnouf, R De Clercq, E A novel mutation (F227L) arises in the reverse transcriptase of human immunodeficiency virus type 1 on dose-escalating treatment of HIV type 1-infected cell cultures with the nonnucleoside reverse transcriptase inhibitor thiocarboxanilide UC-781. |
| title | A novel mutation (F227L) arises in the reverse transcriptase of human immunodeficiency virus type 1 on dose-escalating treatment of HIV type 1-infected cell cultures with the nonnucleoside reverse transcriptase inhibitor thiocarboxanilide UC-781. |
| title_full | A novel mutation (F227L) arises in the reverse transcriptase of human immunodeficiency virus type 1 on dose-escalating treatment of HIV type 1-infected cell cultures with the nonnucleoside reverse transcriptase inhibitor thiocarboxanilide UC-781. |
| title_fullStr | A novel mutation (F227L) arises in the reverse transcriptase of human immunodeficiency virus type 1 on dose-escalating treatment of HIV type 1-infected cell cultures with the nonnucleoside reverse transcriptase inhibitor thiocarboxanilide UC-781. |
| title_full_unstemmed | A novel mutation (F227L) arises in the reverse transcriptase of human immunodeficiency virus type 1 on dose-escalating treatment of HIV type 1-infected cell cultures with the nonnucleoside reverse transcriptase inhibitor thiocarboxanilide UC-781. |
| title_short | A novel mutation (F227L) arises in the reverse transcriptase of human immunodeficiency virus type 1 on dose-escalating treatment of HIV type 1-infected cell cultures with the nonnucleoside reverse transcriptase inhibitor thiocarboxanilide UC-781. |
| title_sort | novel mutation f227l arises in the reverse transcriptase of human immunodeficiency virus type 1 on dose escalating treatment of hiv type 1 infected cell cultures with the nonnucleoside reverse transcriptase inhibitor thiocarboxanilide uc 781 |
| work_keys_str_mv | AT balzarinij anovelmutationf227larisesinthereversetranscriptaseofhumanimmunodeficiencyvirustype1ondoseescalatingtreatmentofhivtype1infectedcellcultureswiththenonnucleosidereversetranscriptaseinhibitorthiocarboxanilideuc781 AT pelemansh anovelmutationf227larisesinthereversetranscriptaseofhumanimmunodeficiencyvirustype1ondoseescalatingtreatmentofhivtype1infectedcellcultureswiththenonnucleosidereversetranscriptaseinhibitorthiocarboxanilideuc781 AT esnoufr anovelmutationf227larisesinthereversetranscriptaseofhumanimmunodeficiencyvirustype1ondoseescalatingtreatmentofhivtype1infectedcellcultureswiththenonnucleosidereversetranscriptaseinhibitorthiocarboxanilideuc781 AT declercqe anovelmutationf227larisesinthereversetranscriptaseofhumanimmunodeficiencyvirustype1ondoseescalatingtreatmentofhivtype1infectedcellcultureswiththenonnucleosidereversetranscriptaseinhibitorthiocarboxanilideuc781 AT balzarinij novelmutationf227larisesinthereversetranscriptaseofhumanimmunodeficiencyvirustype1ondoseescalatingtreatmentofhivtype1infectedcellcultureswiththenonnucleosidereversetranscriptaseinhibitorthiocarboxanilideuc781 AT pelemansh novelmutationf227larisesinthereversetranscriptaseofhumanimmunodeficiencyvirustype1ondoseescalatingtreatmentofhivtype1infectedcellcultureswiththenonnucleosidereversetranscriptaseinhibitorthiocarboxanilideuc781 AT esnoufr novelmutationf227larisesinthereversetranscriptaseofhumanimmunodeficiencyvirustype1ondoseescalatingtreatmentofhivtype1infectedcellcultureswiththenonnucleosidereversetranscriptaseinhibitorthiocarboxanilideuc781 AT declercqe novelmutationf227larisesinthereversetranscriptaseofhumanimmunodeficiencyvirustype1ondoseescalatingtreatmentofhivtype1infectedcellcultureswiththenonnucleosidereversetranscriptaseinhibitorthiocarboxanilideuc781 |