HIV-1 predisposed to acquiring resistance to maraviroc (MVC) and other CCR5 antagonists in vitro has an inherent, low-level ability to utilize MVC-bound CCR5 for entry

Roche, M, Jakobsen, M, Ellett, A, Salimiseyedabad, H, Jubb, B, Westby, M, Lee, B, Lewin, S, Churchill, M and Gorry, P 2011, 'HIV-1 predisposed to acquiring resistance to maraviroc (MVC) and other CCR5 antagonists in vitro has an inherent, low-level ability to utilize MVC-bound CCR5 for entry', Retrovirology, vol. 8, no. 89, pp. 1-7.


Document type: Journal Article
Collection: Journal Articles

Title HIV-1 predisposed to acquiring resistance to maraviroc (MVC) and other CCR5 antagonists in vitro has an inherent, low-level ability to utilize MVC-bound CCR5 for entry
Author(s) Roche, M
Jakobsen, M
Ellett, A
Salimiseyedabad, H
Jubb, B
Westby, M
Lee, B
Lewin, S
Churchill, M
Gorry, P
Year 2011
Journal name Retrovirology
Volume number 8
Issue number 89
Start page 1
End page 7
Total pages 7
Publisher BioMed Central
Abstract Background Maraviroc (MVC) and other CCR5 antagonists are HIV-1 entry inhibitors that bind to- and alter the conformation of CCR5, such that CCR5 is no longer recognized by the viral gp120 envelope (Env) glycoproteins. Resistance to CCR5 antagonists results from HIV-1 Env acquiring the ability to utilize the drug-bound conformation of CCR5. Selecting for HIV-1 resistance to CCR5-antagonists in vitro is relatively difficult. However, the CCR5-using CC1/85 strain appears to be uniquely predisposed to acquiring resistance to several CCR5 antagonists in vitro including MVC, vicriviroc and AD101. Findings Here, we show that Env derived from the parental CC1/85 strain is inherently capable of a low affinity interaction with MVC-bound CCR5. However, this phenotype was only revealed in 293-Affinofile cells and NP2-CD4/CCR5 cells that express very high levels of CCR5, and was masked in TZM-bl, JC53 and U87-CD4/CCR5 cells as well as PBMC, which express comparatively lower levels of CCR5 and which are more commonly used to detect resistance to CCR5 antagonists. Conclusions Env derived from the CC1/85 strain of HIV-1 is inherently capable of a low-affinity interaction with MVC-bound CCR5, which helps explain the relative ease in which CC1/85 can acquire resistance to CCR5 antagonists in vitro. The detection of similar phenotypes in patients may identify those who could be at higher risk of virological failure on MVC.
Subject Medical Virology
DOI - identifier 10.1186/1742-4690-8-89
Copyright notice © 2011 Roche et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ISSN 1742-4690
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 30 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 31 times in Scopus Article | Citations
Altmetric details:
Access Statistics: 28 Abstract Views  -  Detailed Statistics
Created: Mon, 30 May 2016, 08:48:00 EST by Catalyst Administrator
© 2014 RMIT Research Repository • Powered by Fez SoftwareContact us