An increase in viral replicative capacity drives the evolution of protease inhibitor-resistant human immunodeficiency virus type 1 in the absence of drugs

Journal of Acquired Immune Deficiency Syndromes : JAIDS
Noortje M van MaarseveenMonique Nijhuis

Abstract

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 ...Continue Reading

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Citations

Jan 9, 2013·Medical Microbiology and Immunology·Dilek AlpsarBaki Akgül
Aug 28, 2009·The Journal of Antimicrobial Chemotherapy·Esmeralda A SoaresMarcelo A Soares
Apr 20, 2011·The Journal of Antimicrobial Chemotherapy·Marieke PingenAnnemarie M J Wensing
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Jan 23, 2016·The Korean Journal of Parasitology·Shehla KhalilManorama Deb
Jan 16, 2019·The Tohoku Journal of Experimental Medicine·Ke DongXiaofang Pei
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May 31, 2018·Scientific Reports·Natália Mirele CantãoRejane Maria Tommasini Grotto

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