Evolution of gag and gp41 in Patients Receiving Ritonavir-Boosted Protease Inhibitors
Genre
Journal ArticleDate
2017-12-01Author
Manasa, JVarghese, V
Pond, SLK
Rhee, SY
Tzou, PL
Fessel, WJ
Jang, KS
White, E
Rögnvaldsson, T
Katzenstein, DA
Shafer, RW
Subject
AdultEvolution, Molecular
Female
Genotype
HIV Envelope Protein gp41
HIV Infections
HIV Protease Inhibitors
HIV-1
Humans
Male
Middle Aged
Mutation
Ritonavir
Selection, Genetic
Sequence Analysis, DNA
Young Adult
gag Gene Products, Human Immunodeficiency Virus
Permanent link to this record
http://hdl.handle.net/20.500.12613/5109
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Show full item recordDOI
10.1038/s41598-017-11893-8Abstract
© 2017 The Author(s). 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-A nd 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.Citation to related work
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http://dx.doi.org/10.34944/dspace/5091