Abstract: Furthermore, KF116 inhibited the HIV-1 IN variant with the A128T substitution, which confers resistance to the majority of quinoline-based ALLINIs.
Introduction: Furthermore, MINIs inhibited the HIV-1 variant with the A128T IN substitution, which confers resistance to the majority of ALLINIs.
Introduction: In particular, A128T substitution is most common and has been shown to confer marked resistance to the majority of ALLINIs.
Method: The A128T CCD protein was concentrated to 8.5 mg/ml and crystallized at room temperature (20 C) using the hanging drop vapor diffusion method.
Method: The HIV-1 IN CCD (residues 50-212 containing the F185K substitution) and its PMID: 24663024
2014
Antimicrobial agents and chemotherapy
Abstract: Passage of virus in the presence of inhibitor selected for either A128T, A128N, or L102F primary resistance substitutions, all mapping to a conserved allosteric pocket on the catalytic core of integrase.
Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells.
Discussion: that the NCINI resistance-conferring A128T mutation perturbs the ability of NCINIs to bind and promote IN multimerization with minimal impact on IN-LEDGF binding.
The A128T resistance mutation reveals aberrant protein multimerization as the primary mechanism of action of allosteric HIV-1 integrase inhibitors.
PMID: 23615903
2013
The Journal of biological chemistry
Abstract: Accordingly, WT IN catalytic activities and HIV-1 replication were potently inhibited by ALLINIs, whereas the A128T substitution in IN resulted in significant resistance to the inhibitors both in vitro and in cell culture assays.
Abstract: Consequently, the A128T substitution had only a minor effect on the ALLINI IC50 values for IN-LEDGF/p75 binding.
Abstract: Instead, ALLINIs markedly altered the multimerization of IN by promoting aberrant higher order WT (but not A128T) IN oligomers.
Abstract: Selection of viral strains under ALLINI pressure has revealed an A128T substitution in HIV-1 IN as a primary mechanism of
The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions.
Method: We followed-up the 50 mutations of resistance present at 32 positions: associated with in vitro or in vivo resistance to HIV-1 integrase inhibitors: H51Y, T66I/A/K, V72I, L74I/A/M, E92Q, T97A, T112I, F121Y, T125K, A128T, E138 K/A/D, G140R/C/H, Y143C/H/R, Q146K/P, S147G, Q148K/R/H, V151I, PMID: 18715920
2008
Journal of virology
Abstract: In addition, mutations that do not confer reduced susceptibility when present alone (H114Y, L74M, R20K, A128T, E138K, and S230R) are also discussed in relation to their position in the catalytic core domain and their proximity to known structural features of integrase.
Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors.
Discussion: Mutations that have been selected in vitro or in vivo primarily by earlier INI compounds such as L-708,906, S-1360, and L-870,810 but which appear to be less essential for raltegravir or elvitegravir resistance include the highly polymorphic mutations V72I, V165I, and V201I; the minimally polymorphic mutation M154I; and the nonpolymorphic mutations T125K, A128T, and K160D.
Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV.
Discussion: The reduced replication kinetics of the mutated virus were further analyzed by quantitative PCR analysis of 293T cells infected with VSV-G pseudotyped A128T/E170G virus.
Discussion: Two mutations were detected in the IN coding region at key positions in the LEDGF/p75-IN interface (A128T and E170G) (Figure 1).
Discussion: Whereas the number of 2-LTR circles produced by WT virus increased more than 10-fold in the 293T eGFP-Delta325 cells (Figure S2E) as a result of the defect in integration (Figure S2F), the number of 2-LTR circles returned to almost normal levels when the cells were infected with A128T/E170G virus.
Natural polymorphism of the HIV-1 integrase gene and mutations associated with integrase inhibitor resistance.
Abstract: Of the 42 aa substitutions currently associated with INI resistance, 21 occurred as natural polymorphisms: V72I, L74I, T97A, T112I, A128T, E138K, Q148H, V151I, S153Y/A, M154I, N155H, K156N, E157Q, G163R, V165I, V201I, I203M, T206S, S230N and R263K.
HIV mutation literature information.
PMID: 
2014
PLoS pathogens
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