کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1994230 | 1064753 | 2009 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Selection and analysis of HIV-1 integrase strand transfer inhibitor resistant mutant viruses
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
This report describes methods for the selection and analysis of antiretroviral resistance to HIV integrase strand transfer inhibitors (InSTIs) in cell culture. The method involves the serial passage of HIV-1 in the presence of increasing concentrations of test inhibitors, followed by the cloning and sequencing of the integrase coding region from the selected viruses. The identified mutations are subsequently re-engineered into a reference wild-type molecular clone, and the resulting replication capacity and level of drug resistance are determined relative to the wild-type virus. Here we describe examples of selection and analysis of InSTI-resistant viruses using four integrase inhibitors from three structurally distinct chemical classes; a diketo acid, two naphthyridines, and a pyrimidinecarboxamide. Each inhibitor selected an independent route to resistance. Interestingly, the shift in the IC50 required to suppress the re-engineered resistant mutant viruses closely matched the concentration of compound used during the selection of drug resistance.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Methods - Volume 47, Issue 4, April 2009, Pages 277-282
Journal: Methods - Volume 47, Issue 4, April 2009, Pages 277-282
نویسندگان
Marc Witmer, Robert Danovich,