October 15, 2001Journal of Virology
Resistance to Nucleoside Analog Reverse Transcriptase Inhibitors Mediated by Human Immunodeficiency Virus Type 1 p6 Protein
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Discussion
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Implication
Observational and molecular study reveals PTAP motif duplications in HIV-1 p6 mediate NRTI resistance in treated patients, suggesting target-independent escape via enzyme packaging.
Key Points
- To determine whether mutations outside the viral target gene, specifically in the HIV-1 p1-p6(gag)-p6(pol) region, confer resistance to nucleoside analog reverse transcriptase inhibitors.
- Sequenced and analyzed the p1-p6(gag)-p6(pol) viral region from 222 NRTI-treated patients and treatment-naive controls.
- Constructed molecular clones with an APPAPP duplication in p6(Gag) to evaluate viral protein maturation, reverse transcriptase packaging, and replication fitness under NRTI pressure.
- Duplication of the proline-rich PTAP motif occurred in plasma virus from 47 of 222 (21.2%) NRTI-treated patients, while occurring very rarely in drug-naive individuals.
- Molecular clones carrying the duplication packaged 34% excess reverse transcriptase and displayed a competitive growth advantage in the presence of NRTIs despite delayed protein maturation.
Cite This Study
Peters et al. (2001) studied this question.