Evolution of gag and gp41 in Patients Receiving Ritonavir-Boosted Protease Inhibitors.

TitleEvolution of gag and gp41 in Patients Receiving Ritonavir-Boosted Protease Inhibitors.
Publication TypeJournal Article
Year of Publication2017
AuthorsManasa J, Varghese V, Pond SLKosakovs, Rhee S-Y, Tzou PL, W Fessel J, Jang KS, White E, Rögnvaldsson T, Katzenstein DA, Shafer RW
JournalSci Rep
Volume7
Issue1
Pagination11559
Date Published2017 Sep 14
ISSN2045-2322
Abstract

Several groups have proposed that genotypic determinants in gag and the gp41 cytoplasmic domain (gp41-CD) reduce protease inhibitor (PI) susceptibility without PI-resistance mutations in protease. However, no gag and gp41-CD mutations definitively responsible for reduced PI susceptibility have been identified in individuals with virological failure (VF) while receiving a boosted PI (PI/r)-containing regimen. To identify gag and gp41 mutations under selective PI pressure, we sequenced gag and/or gp41 in 61 individuals with VF on a PI/r (n = 40) or NNRTI (n = 20) containing regimen. We quantified nonsynonymous and synonymous changes in both genes and identified sites exhibiting signal for directional or diversifying selection. We also used published gag and gp41 polymorphism data to highlight mutations displaying a high selection index, defined as changing from a conserved to an uncommon amino acid. Many amino acid mutations developed in gag and in gp41-CD in both the PI- and NNRTI-treated groups. However, in neither gene, were there discernable differences between the two groups in overall numbers of mutations, mutations displaying evidence of diversifying or directional selection, or mutations with a high selection index. If gag and/or gp41 encode PI-resistance mutations, they may not be confined to consistent mutations at a few sites.

DOI10.1038/s41598-017-11893-8
Alternate JournalSci Rep
PubMed ID28912582
PubMed Central IDPMC5599673
Grant ListR01 AI068581 / AI / NIAID NIH HHS / United States
R21 AI102792 / AI / NIAID NIH HHS / United States
R25 TW009338 / TW / FIC NIH HHS / United States