Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
J Gen Virol. 2013 Jul;94(Pt 7):1597-1607. doi: 10.1099/vir.0.050914-0. Epub 2013 Mar 27.
The fitness of non-nucleoside reverse transcriptase inhibitor (NNRTI) drug-resistant reverse transcriptase (RT) mutants of HIV-1 correlates with the amount of RT in the virions and the RNase H activity of the RT. We wanted to understand the mechanism by which secondary NNRTI-resistance mutations, L100I and K101E, and the nucleoside resistance mutation, L74V, alter the fitness of K103N and G190S viruses. We measured the amount of RT in virions and the polymerization and RNase H activities of mutant RTs compared to wild-type, K103N and G190S. We found that L100I, K101E and L74V did not change the polymerization or RNase H activities of K103N or G190S RTs. However, L100I and K101E reduced the amount of RT in the virions and subsequent addition of L74V restored RT levels back to those of G190S or K103N alone. We conclude that fitness changes caused by L100I, K101E and L74V derive from their effects on RT content.
HIV-1 非核苷类逆转录酶抑制剂（NNRTI）耐药逆转录酶（RT）突变体的适应性与病毒粒子中的 RT 含量和 RT 的 RNase H 活性相关。我们希望了解次要 NNRTI 耐药突变 L100I 和 K101E 以及核苷耐药突变 L74V 如何改变 K103N 和 G190S 病毒的适应性。我们测量了病毒粒子中 RT 的含量以及与野生型、K103N 和 G190S 相比突变 RT 的聚合和 RNase H 活性。我们发现 L100I、K101E 和 L74V 并未改变 K103N 或 G190S RT 的聚合或 RNase H 活性。然而，L100I 和 K101E 降低了病毒粒子中的 RT 含量，随后添加 L74V 将 RT 水平恢复到仅 G190S 或 K103N 的水平。我们得出结论，L100I、K101E 和 L74V 引起的适应性变化源于它们对 RT 含量的影响。
