Molecular gymnastics: Mechanisms of HIV-1 resistance to CCR5 antagonists and impact on virus phenotypes

Roche, M, Borm, K, Flynn, J, Lewin, S, Churchill, M and Gorry, P 2016, 'Molecular gymnastics: Mechanisms of HIV-1 resistance to CCR5 antagonists and impact on virus phenotypes', Current Topics in Medicinal Chemistry, vol. 16, no. 30, pp. 1-16.


Document type: Journal Article
Collection: Journal Articles

Title Molecular gymnastics: Mechanisms of HIV-1 resistance to CCR5 antagonists and impact on virus phenotypes
Author(s) Roche, M
Borm, K
Flynn, J
Lewin, S
Churchill, M
Gorry, P
Year 2016
Journal name Current Topics in Medicinal Chemistry
Volume number 16
Issue number 30
Start page 1
End page 16
Total pages 16
Publisher Bentham Science Publishers
Abstract Human immunodeficiency virus type 1 (HIV-1) enters host cells through the binding of its envelope glycoproteins (Env) to the host cell receptor CD4 and then subsequent binding to a chemokine coreceptor, either CCR5 or CXCR4. CCR5 antagonists are a relatively recent class addition to the armamentarium of anti-HIV-1 drugs. These compounds act by binding to a hydrophobic pocket formed by the transmembrane helices of CCR5 and altering the conformation of the extracellular domains, such that they are no longer recognized by Env. Maraviroc is the first drug within this class to be licenced for use in HIV-1 therapy regimens. HIV resistance to CCR5 antagonists occurs either through outgrowth of pre-existing CXCR4-using viruses, or through acquisition of the ability of CCR5-using HIV-1 to use the antagonist bound form of CCR5. In the latter scenario, the mechanism underlying resistance is through complex alterations in the way that resistant Envs engage CCR5. These significant changes are unlikely to occur without consequence to the viral entry phenotype and may also open up new avenues to target CCR5 antagonist resistant viruses. This review discusses the mechanism of action of CCR5 antagonists, how HIV resistance to CCR5 antagonists occurs, and the subsequent effects on Env function.
Subject Virology
Medical Virology
Infectious Diseases
Keyword(s) HIV-1
Envelope
CCR5
Maraviroc
Tropism
Resistance
DOI - identifier 10.2174/1568026615666150901114724
Copyright notice © 2016 Bentham Science Publishers
ISSN 1568-0266
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 2 times in Scopus Article | Citations
Altmetric details:
Access Statistics: 62 Abstract Views  -  Detailed Statistics
Created: Fri, 04 Mar 2016, 10:25:00 EST by Catalyst Administrator
© 2014 RMIT Research Repository • Powered by Fez SoftwareContact us