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. 2012 Jan 19;8(1):e1002359. doi: 10.1371/journal.pcbi.1002359

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von Kleist et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.

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A: Cell-specific factors: Concentration response curve of ddATP for wild type RT during DNA-dependent polymerization (homo-polymeric sequence) in unstimulated T-cells (solid line) and the impact of a 100-fold variation of the the intracellular nucleoside concentrations (dotted line). The illustration was generated by evaluating eq. (19) and typical parameters for DNA-dependent polymerization during HIV-1 reverse transcription and its inhibition by ddATP (all parameters are indicated in Table 1 and Table S1, supplementary material). The corresponding is depicted by a green filled circle. B: Molecular mechanisms of drug resistance and hyper-susceptibility (dashed lines). Impact of (i) selective attrition of inhibitor incorporation and (ii) selective attrition of inhibitor binding to the primer-template on drug susceptibility. Hypersusceptibility is conferred by the opposite change in the indicated parameters. In order to generate the dashed lines, the respective parameters have been increased/decreased by a factor of 100.

Inline graphic — A: Cell-specific factors: Concentration response curve of ddATP for wild type RT during DNA-dependent polymerization (homo-polymeric sequence) in unstimulated T-cells (solid line) and the impact of a 100-fold variation of the the intracellular nucleoside concentrations (dotted line). The illustration was generated by evaluating eq. (19) and typical parameters for DNA-dependent polymerization during HIV-1 reverse transcription and its inhibition by ddATP (all parameters are indicated in Table 1 and Table S1, supplementary material). The corresponding is depicted by a green filled circle. B: Molecular mechanisms of drug resistance and hyper-susceptibility (dashed lines). Impact of (i) selective attrition of inhibitor incorporation and (ii) selective attrition of inhibitor binding to the primer-template on drug susceptibility. Hypersusceptibility is conferred by the opposite change in the indicated parameters. In order to generate the dashed lines, the respective parameters have been increased/decreased by a factor of 100.