Investigating human immunodeficiency virus resistance mechanisms to D-Peptide entry inhibitors

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Title Investigating human immunodeficiency virus resistance mechanisms to D-Peptide entry inhibitors
Publication Type dissertation
School or College School of Medicine
Department Biochemistry
Author Smith, Amanda Ray
Date 2018
Description The PIE series of D-peptide HIV entry inhibitors, PIE12-trimer and Chol-PIE12-trimer (CPT31), inhibit a wide range of HIV isolates with pM potency while also exhibiting a high barrier to resistance. Here, we show that HIV acquires a primary PIE12 resistance mutation (Q577R/N/K) in both in vitro and in vivo resistance models. Development of this resistance mutation comes at a significant fitness cost to the virus, but the virus also acquires a set of compensatory mutations that rescue this fitness defect. We also show that CPT31 is an effective therapeutic against SHIV infection in rhesus macaques in both treatment and preventative contexts. These data indicate that CPT31 is a promising clinical candidate and could provide a novel agent with a unique mechanism of action against HIV.
Type Text
Publisher University of Utah
Subject Virology
Dissertation Name Doctor of Philosophy
Language eng
Rights Management (c) Amanda Ray Smith
Format application/pdf
Format Medium application/pdf
ARK ark:/87278/s6hx68p1
Setname ir_etd
ID 1486758
Reference URL https://collections.lib.utah.edu/ark:/87278/s6hx68p1
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