BACKGROUND: Protease (PR) inhibitors (PIs) were designed against subtype B virus of human immunodeficiency virus type 1 (HIV-1), but believed to retain its activity against most of the other subtypes. CRF01_AE PR (AE-PR) contains background mutations that are presumed to alter the drug susceptibility of PR. In addition, amino acid variations found in HIV-1 Gag potentially affect the drug susceptibility or catalytic efficiency of PR. METHODS: We studied the impact of naturally occurring amino acid substitutions found in AE-PR and CRF01_AE Gag (AE-Gag) on the drug susceptibility of PR to 9 currently available PIs, using the pNL4-3-derived luciferase reporter virus containing AE-Gag and/or AE-PR genes derived from drug treatment-naïve, HIV-1-infected Thai patients. RESULTS: Sequencing analysis revealed that several mutations were detected in deduced amino acid sequences of AE-PR and AE-Gag genes, as compared to these genes of pNL4-3. Drug susceptibility tests revealed that AE-PR showed a variety of susceptibilities to 9 PIs compared with pNL4-3 PR. In addition, AE-Gag significantly reduced the drug susceptibility of AE-PR and pNL4-3 PR. CONCLUSION: Our results suggest that amino acid variations in AE-PR and AE-Gag play roles in determining the drug susceptibility of CRF01_AE viruses to PIs.
BACKGROUND: Protease (PR) inhibitors (PIs) were designed against subtype B virus of human immunodeficiency virus type 1 (HIV-1), but believed to retain its activity against most of the other subtypes. CRF01_AE PR (AE-PR) contains background mutations that are presumed to alter the drug susceptibility of PR. In addition, amino acid variations found in HIV-1Gag potentially affect the drug susceptibility or catalytic efficiency of PR. METHODS: We studied the impact of naturally occurring amino acid substitutions found in AE-PR and CRF01_AE Gag (AE-Gag) on the drug susceptibility of PR to 9 currently available PIs, using the pNL4-3-derived luciferase reporter virus containing AE-Gag and/or AE-PR genes derived from drug treatment-naïve, HIV-1-infected Thaipatients. RESULTS: Sequencing analysis revealed that several mutations were detected in deduced amino acid sequences of AE-PR and AE-Gag genes, as compared to these genes of pNL4-3. Drug susceptibility tests revealed that AE-PR showed a variety of susceptibilities to 9PIs compared with pNL4-3 PR. In addition, AE-Gag significantly reduced the drug susceptibility of AE-PR and pNL4-3 PR. CONCLUSION: Our results suggest that amino acid variations in AE-PR and AE-Gag play roles in determining the drug susceptibility of CRF01_AE viruses to PIs.
Authors: Lucile Larrouy; C Chazallon; R Landman; C Capitant; G Peytavin; G Collin; C Charpentier; A Storto; G Pialoux; C Katlama; P M Girard; P Yeni; J P Aboulker; F Brun-Vezinet; D Descamps Journal: Antimicrob Agents Chemother Date: 2010-05-03 Impact factor: 5.191
Authors: Chris M Parry; Madhavi Kolli; Richard E Myers; Patricia A Cane; Celia Schiffer; Deenan Pillay Journal: Antimicrob Agents Chemother Date: 2010-12-13 Impact factor: 5.191
Authors: Saran Vardhanabhuti; David Katzenstein; John Bartlett; Nagalingeswaran Kumarasamy; Carole L Wallis Journal: Open Forum Infect Dis Date: 2016-08-24 Impact factor: 3.835
Authors: Justen Manasa; Vici Varghese; Sergei L Kosakovsky Pond; Soo-Yon Rhee; Philip L Tzou; W Jeffrey Fessel; Karen S Jang; Elizabeth White; Thorsteinn Rögnvaldsson; David A Katzenstein; Robert W Shafer Journal: Sci Rep Date: 2017-09-14 Impact factor: 4.379
Authors: Katherine A Sutherland; Chris M Parry; Adele McCormick; Anne Kapaata; Fred Lyagoba; Pontiano Kaleebu; Charles F Gilks; Ruth Goodall; Moira Spyer; Cissy Kityo; Deenan Pillay; Ravindra K Gupta Journal: PLoS One Date: 2015-09-18 Impact factor: 3.240
Authors: K A Sutherland; J Ghosn; J Gregson; J L Mbisa; M L Chaix; I Cohen Codar; J F Delfraissy; C Delaugerre; R K Gupta Journal: J Antimicrob Chemother Date: 2014-09-16 Impact factor: 5.790