Yeast cells as a tool for analysis of HIV-1 protease susceptibility to protease inhibitors, a comparative study

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• 作者：Isabelle Ravaux ; Christelle Perrin-East ; Coralie Attias ; Jacqueline Cottalorda ; Jacques Durant ; Pierre Dellamonica ; Pablo Gluschankof ; Andreas Stein ; Catherine Tamalet
• 关键词：PI ; protease inhibitor ; LPV/r ; boosted Lopinavir ; NFV ; Nelfinavir ; ATV/r ; boosted Atazanavir ; FPV ; Fosamprenavir ; SQV/r ; Saquinavir boosted saquinavir ; DRV/r ; boosted Darunavir
• 刊名：Journal of Virological Methods
• 出版年：January, 2014
• 年：2014
• 卷：195
• 期：Complete
• 页码：180-184
• 全文大小：235 K

文摘

HIV develops drug resistance at a high rate under drug selection pressure. Resistance tests are recommended to help physicians optimize antiretroviral drug therapies. For this purpose, genotypic and phenotypic tests have been developed. In order to propose a new phenotypic test that will be less laborious, expensive, and time consuming than the standard ones, a new procedure to measure HIV-1 protease susceptibility to protease inhibitor (PIs) in Saccharomyces cerevisiae yeast cells was developed. This procedure is based on HIV-1 protease expression in yeast. While the viral protein induces yeast cell death, its inhibition by PIs in the culture medium allows the cell to grow in a dose-dependent manner. In a comparative study of standard genotypic analysis vs. yeast cell-based phenotypic tests, performed on HIV-1 protease coding DNA in 17 different plasma samples from infected individuals, a clear match was found between the results obtained using the two technologies. This suggests that the yeast-based procedure is at least as accurate as standard genotypic test in defining susceptibility to protease inhibitors. This encouraging result should be the basis for large-scale validation of the new phenotypic resistance test.