V3 determinants of HIV-1 escape from the CCR5 inhibitors Maraviroc and Vicriviroc
| Autor: | Rogier W. Sanders, Per Johan Klasse, Martin R. Jakobsen, Paul R Gorry, John P. Moore, Reem Berro |
|---|---|
| Přispěvatelé: | Amsterdam institute for Infection and Immunity, Medical Microbiology and Infection Prevention |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Receptors CCR5 Protein Conformation Vicriviroc Small molecule CCR5 inhibitors Molecular Sequence Data Human immunodeficiency virus (HIV) Biology HIV Envelope Protein gp120 medicine.disease_cause Article Piperazines Maraviroc V3 sequence 03 medical and health sciences chemistry.chemical_compound Protein structure Cyclohexanes HIV Fusion Inhibitors Virology Drug Resistance Viral medicine HIV fusion inhibitors Amino Acid Sequence Peptide sequence CCR5 NT 030304 developmental biology chemistry.chemical_classification Genetics 0303 health sciences 030306 microbiology Resistance pattern virus diseases Triazoles Peptide Fragments 3. Good health Amino acid body regions Pyrimidines chemistry Drug resistance CCR5 Receptor Antagonists HIV-1 sense organs CCR5 medicine.drug |
| Zdroj: | Berro, R, Klasse, P J, Jakobsen, M R, Gorry, P R, Moore, J P & Sanders, R W 2012, ' V3 determinants of HIV-1 escape from the CCR5 inhibitors Maraviroc and Vicriviroc ', Virology, vol. 427, no. 2, pp. 158-65 . https://doi.org/10.1016/j.virol.2012.02.006 Virology, 427(2), 158-165. Academic Press Inc. Virology |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2012.02.006 |
| Popis: | HIV-1 develops resistance to CCR5 antagonists such as Maraviroc (MVC) and Vicriviroc (VVC) both in vitro and in vivo, with most changes arising in the gp120 V3 region. Both compounds bind to the same hydrophobic cavity in CCR5 in subtly different ways. Here, we investigated which V3 sequence changes are most associated with MVC and VVC resistance and how they affect the interaction between gp120 and the CCR5 NT. We found that WCand MVC-selected amino acid changes map to different V3 locations and involve residues that interact with the CCR5 NT in different ways. Changes in VVC-selected, but not MVC-selected, variants often involve charged residues. Although the overall V3 charge tends not to change, the introduction or removal of charged residues at specific positions affects the local electrostatic potential and could have structural and functional implications. In summary, VVC and MVC trigger the evolution of distinct HIV-1 resistance patterns in V3. (C) 2012 Elsevier Inc. All rights reserved |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect