Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa.
PMID: 26258548
2015
AIDS research and human retroviruses
Abstract: Before bPI, significant variation in Protease and Gag was observed at positions previously associated with PI exposure and resistance including Gag mutations L449P, S451N, and L453P and Protease K20I an
Introduction: Of particular relevance to this study were mutations associated with resistance to boosted lopinavir: L10I (three subtype A patients), L10V (one subtype A), K20R (five subtype As and 1 subtype C), L33V (one subtype D), L63P (one subtype A, two subtype Cs, and three subtype Ds).
Conformational variation of an extreme drug resistant mutant of HIV protease.
PMID: 26397743
2015
Journal of molecular graphics & modelling
Method: Plasmid DNA encoding PR (subtype B of group M) with 20 mutations Q7K; L10F; I13V; I15V; D30N; V32I; L33F; E35D; M36I; S37N; I47V; I54L; Q58E; I62V; L63P; A71V; I84V; N88D; L89T and L90M (termed PR20) cloned between the Nde1 and BamH1 sites
The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil.
Result: In contrast, several secondary mutations were found to differ between B and non-B subtypes: L63P (p < 0.001) and A71T (p = 0.021) were higher in subtype B, and M36I (p < 0.001), K20R (p < 0.001), L10V (p = 0.004), L89 M (p < 0.001), and F53L (p = 0.011) were higher in non-B subtypes.
Result: With respect to accessory or secondary mutations, the most frequent were L63P (60.7%), M36I (41.1%), I93L (40.1%), I62V (39%), V77I (35.8%), A71V (24.9%), and L10I (24.7%) (Figure 1(d)).
Discussion: L63P and
HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users.
Abstract: Minor PI mutations including A71T, G48E, G48R, I13V, K20I, K20R, L10I, L10V, L33F, L63P, T74S, V11I, and V32L were detected among the ART-experienced (36.2 vs.
Table: L63P
Discussion: In addition, our results corroborate previous studies showing K20I/M/R, L10I/V, I13V, and L63P minor mutations among
HIV-1 subtype characteristics of infected persons living in southwestern Greece.
Result: Finally, several polymorphic sites were identified, with L63PSA being the most prevalent (96% of cases).
The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops.
PMID: 29124158
2015
Biochemistry and biophysics reports
Method: MDR769 L33F is based on the previously studied multi-drug resistant variant 769, MDR769, which contains the mutations Q7K, L10I, M36V, M46L, I54V, I62V, L63P, A71V, V82T, I84V, L90M.
Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling.
Introduction: The effects of the single secondary mutations, L63P, on the conformational sampling of subtype B (LAI) sequence was also investigated because it is a common natural polymorphism contained within the PRE sequence.
Method: L63P for NMR studies did not contain the K55C mutation.
Method: Buffers were adjusted to pH 9.06 for PRE and POST and pH 9.39 for L63P.
Method: Given that the L63P construct contains only one mutation compared to subtype B, assignments were made based upon previously published results.
Method: Relaxation measurements were performed on 15N L63P at 600 MHz and 700 MHz as described previously.
Method: The L63P construct was generated using site-directed mutagenesis kit (Strategene) and made w
Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis.
Result: According to the IAS-USA, the mutations associated with drug resistance, with a p >10%, were L10I, M36I, I62V, L63P, I64V, A71V/T, V77I, L90M, and I93L.
Result: Although the study of mutations in this position has been limited to L63P to assess the effect of mutations that provide non-hydrophobic characteristics, alternative mechanisms could be shown by which HIV-1 PR compensates for pharmacological stressors.
Result: The L63P mutation has a compensatory effect that increases catalytic activity from 110% to 530%; when L63P is
Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China.
Abstract: Polymorphism mutation sites with mutation rates in the protease region higher than 60.0% were: L63A/P/S/T 89.7%, V77I 82.2%, I72E/M/K/T/V 80.4%, I93L 75.7%, and E35D 72.9%.
Result: The sites with mutation rates higher than 60.0% included: L63A/P/S/T 89.7% (96/107), among which L63P was 70.1% (75/107); V77I 82.2% (88/107); I72E/M/K/T/V 80.4% (86/107), among which I72V was 63.6% (75/107); I93L 75.7%; E35D 72.9%.
Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps.
Method: The PRP51 construct contains 14 mutations (L10I, I15V, K20R, L24I, V32I, L33F, M36I, M46L, I54M, L63P, K70Q, V82I, I84V, and L89M) plus three other mutations Q7K to minimize autoproteolysis and C67A and C95A to prevent cysteine-induced aggregation.
Result: Mutations L63P and K70Q also alter surface si
HIV mutation literature information.
PMID: 
2015
AIDS research and human retroviruses
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