van Maarseveen Noortje M, de Jong Dorien, Boucher Charles A B, Nijhuis Monique
Department of Virology, Eijkman-Winkler Center, University Medical Center Utrecht, Utrecht, The Netherlands.
J Acquir Immune Defic Syndr. 2006 Jun;42(2):162-8. doi: 10.1097/01.qai.0000219787.65915.56.
Little is known about the factors which drive the evolution of protease inhibitor-resistant human immunodeficiency virus type-1 in the absence of drugs. To examine if viral replicative capacity (RC) is an important determinant, we performed in vitro evolution experiments in the absence of drugs with a unique panel of 6 drug-resistant human immunodeficiency virus type-1 recombinant protease variants with a range of different RC. The experiments revealed that an increase in viral RC was indeed an important determinant of evolution. Initial protease inhibitor-resistant viruses with only a few protease mutations and a lowered RC evolved into viruses with an increased RC, either by reversion of primary resistance mutations or by the acquisition of compensatory mutations. For these viruses with a lowered RC, higher fitness peaks are most likely available in the sequence space. Evolution of these viruses in the absence of drugs will therefore drive them to new fitness peaks. In contrast, viruses with an RC comparable to wild type or even higher than wild type did not show any evolution. In the case of these viruses, it is not so likely that higher fitness peaks are present within the sequence space, and therefore, these variants will persist in the absence of drug pressure.
关于在无药物情况下驱动抗蛋白酶抑制剂的1型人类免疫缺陷病毒进化的因素，人们了解甚少。为了检验病毒复制能力（RC）是否是一个重要的决定因素，我们在无药物的情况下，对一组独特的6种具有不同RC范围的抗药1型人类免疫缺陷病毒重组蛋白酶变体进行了体外进化实验。实验表明，病毒RC的增加确实是进化的一个重要决定因素。最初只有少数蛋白酶突变且RC降低的抗蛋白酶抑制剂病毒，通过初级抗性突变的回复或补偿性突变的获得，进化为RC增加的病毒。对于这些RC降低的病毒，在序列空间中很可能存在更高的适应性峰值。因此，这些病毒在无药物情况下的进化将驱使它们达到新的适应性峰值。相比之下，RC与野生型相当甚至高于野生型的病毒没有表现出任何进化。对于这些病毒，在序列空间中不太可能存在更高的适应性峰值，因此，这些变体在无药物压力的情况下将持续存在。
