The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions.
Resistance to HIV-1 integrase (IN) inhibitor raltegravir (RAL), is encoded by mutations in the IN region of the pol gene. The emergence of the N155H mutation was replaced by a pattern including the Y143R/C/H mutations in three patients with anti-HIV treatment failure. Cloning analysis of the IN gene...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2859942?pdf=render |
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| author | Sandrine Reigadas Guerric Anies Bernard Masquelier Christina Calmels Lieven J Stuyver Vincent Parissi Herve Fleury Marie-Line Andreola |
| author_facet | Sandrine Reigadas Guerric Anies Bernard Masquelier Christina Calmels Lieven J Stuyver Vincent Parissi Herve Fleury Marie-Line Andreola |
| author_sort | Sandrine Reigadas |
| collection | DOAJ |
| description | Resistance to HIV-1 integrase (IN) inhibitor raltegravir (RAL), is encoded by mutations in the IN region of the pol gene. The emergence of the N155H mutation was replaced by a pattern including the Y143R/C/H mutations in three patients with anti-HIV treatment failure. Cloning analysis of the IN gene showed an independent selection of the mutations at loci 155 and 143. Characterization of the phenotypic evolution showed that the switch from N155H to Y143C/R was linked to an increase in resistance to RAL. Wild-type (WT) IN and IN with mutations Y143C or Y143R were assayed in vitro in 3'end-processing, strand transfer and concerted integration assays. Activities of mutants were moderately impaired for 3'end-processing and severely affected for strand transfer. Concerted integration assay demonstrated a decrease in mutant activities using an uncleaved substrate. With 3'end-processing assay, IC(50) were 0.4 microM, 0.9 microM (FC = 2.25) and 1.2 microM (FC = 3) for WT, IN Y143C and IN Y143R, respectively. An FC of 2 was observed only for IN Y143R in the strand transfer assay. In concerted integration, integrases were less sensitive to RAL than in ST or 3'P but mutants were more resistant to RAL than WT. |
| first_indexed | 2024-12-13T21:20:17Z |
| format | Article |
| id | doaj.art-c6ac617748ef4c2897a83543ffe133ac |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T21:20:17Z |
| publishDate | 2010-01-01 |
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| spelling | doaj.art-c6ac617748ef4c2897a83543ffe133ac2022-12-21T23:31:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0154e1031110.1371/journal.pone.0010311The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions.Sandrine ReigadasGuerric AniesBernard MasquelierChristina CalmelsLieven J StuyverVincent ParissiHerve FleuryMarie-Line AndreolaResistance to HIV-1 integrase (IN) inhibitor raltegravir (RAL), is encoded by mutations in the IN region of the pol gene. The emergence of the N155H mutation was replaced by a pattern including the Y143R/C/H mutations in three patients with anti-HIV treatment failure. Cloning analysis of the IN gene showed an independent selection of the mutations at loci 155 and 143. Characterization of the phenotypic evolution showed that the switch from N155H to Y143C/R was linked to an increase in resistance to RAL. Wild-type (WT) IN and IN with mutations Y143C or Y143R were assayed in vitro in 3'end-processing, strand transfer and concerted integration assays. Activities of mutants were moderately impaired for 3'end-processing and severely affected for strand transfer. Concerted integration assay demonstrated a decrease in mutant activities using an uncleaved substrate. With 3'end-processing assay, IC(50) were 0.4 microM, 0.9 microM (FC = 2.25) and 1.2 microM (FC = 3) for WT, IN Y143C and IN Y143R, respectively. An FC of 2 was observed only for IN Y143R in the strand transfer assay. In concerted integration, integrases were less sensitive to RAL than in ST or 3'P but mutants were more resistant to RAL than WT.http://europepmc.org/articles/PMC2859942?pdf=render |
| spellingShingle | Sandrine Reigadas Guerric Anies Bernard Masquelier Christina Calmels Lieven J Stuyver Vincent Parissi Herve Fleury Marie-Line Andreola The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. PLoS ONE |
| title | The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. |
| title_full | The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. |
| title_fullStr | The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. |
| title_full_unstemmed | The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. |
| title_short | The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. |
| title_sort | hiv 1 integrase mutations y143c r are an alternative pathway for resistance to raltegravir and impact the enzyme functions |
| url | http://europepmc.org/articles/PMC2859942?pdf=render |
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